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Quantum Mechanical and Molecular Mechanics Modeling of Membrane-Embedded Rhodopsins

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Abstract

Computational chemistry provides versatile methods for studying the properties and functioning of biological systems at different levels of precision and at different time scales. The aim of this article is to review the computational methodologies that are applicable to rhodopsins as archetypes for photoactive membrane proteins that are of great importance both in nature and in modern technologies. For each class of computational techniques, from methods that use quantum mechanics for simulating rhodopsin photophysics to less-accurate coarse-grained methodologies used for long-scale protein dynamics, we consider possible applications and the main directions for improvement.

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Adapted from Mertz et al. (2011) with permission from Elsevier

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Adapted from Leioatts et al. (2014) with permission from ACS

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Adapted from Salas-Estrada et al. (2018) with permission from Elsevier

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References

  • Ahuja S, Crocker E, Eilers M, Hornak V, Hirshfeld A, Ziliox M, Syrett N, Reeves PJ, Khorana HG, Sheves M, Smith SO (2009a) Location of the retinal chromophore in the activated state of rhodopsin. J Biol Chem 284:10190–10201

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ahuja S, Hornak V, Yan EC, Syrett N, Goncalves JA, Hirshfeld A, Ziliox M, Sakmar TP, Sheves M, Reeves PJ, Smith SO, Eilers M (2009b) Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation. Nat Struct Mol Biol 16:168–175

    CAS  PubMed  PubMed Central  Google Scholar 

  • Alford RF, Leaver-Fay A, Jeliazkov JR, O’Meara MJ, DiMaio FP, Park H, Shapovalov MV, Renfrew PD, Mulligan VK, Kappel K, Labonte JW, Pacella MS, Bonneau R, Bradley P, Dunbrack RL Jr, Das R, Baker D, Kuhlman B, Kortemme T, Gray JJ (2017) The Rosetta all-atom energy function for macromolecular modeling and design. J Chem Theory Comput 13:3031–3048

    CAS  PubMed  PubMed Central  Google Scholar 

  • Altun A, Yokoyama S, Morokuma K (2008a) Mechanism of spectral tuning going from retinal in vacuo to bovine rhodopsin and its mutants: multireference ab initio quantum mechanics/molecular mechanics studies. J Phys Chem B 112:16883–16890

    CAS  PubMed  PubMed Central  Google Scholar 

  • Altun A, Yokoyama S, Morokuma K (2008b) Spectral tuning in visual pigments: an ONIOM (QM: MM) study on bovine rhodopsin and its mutants. J Phys Chem B 112:6814–6827

    CAS  PubMed  PubMed Central  Google Scholar 

  • Amora TL, Ramos LS, Galan JF, Birge RR (2008) Spectral tuning of deep red cone pigments. Biochemistry 47:4614–4620

    CAS  PubMed  Google Scholar 

  • Andruniów T, Ferré N, Olivucci M (2004) Structure, initial excited-state relaxation, and energy storage of rhodopsin resolved at the multiconfigurational perturbation theory level. Proc Natl Acad Sci USA 101:17908–17913

    PubMed  PubMed Central  Google Scholar 

  • Ardevol A, Hummer G (2018) Retinal isomerization and water-pore formation in channelrhodopsin-2. Proc Natl Acad Sci USA 115:3557–3562

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ayton GS, Noid WG, Voth GA (2007) Multiscale modeling of biomolecular systems: in serial and in parallel. Curr Opin Struct Biol 17:192–198

    CAS  PubMed  Google Scholar 

  • Balabin IA, Yang W, Beratan DN (2009) Coarse-grained modeling of allosteric regulation in protein receptors. Proc Natl Acad Sci USA 106:14253–14258

    CAS  PubMed  PubMed Central  Google Scholar 

  • Barducci A, Bussi G, Parrinello M (2008) Well-tempered metadynamics: a smoothly converging and tunable free-energy method. Phys Rev Lett 100:020603

    PubMed  Google Scholar 

  • Baudry J, Crouzy S, Roux B, Smith JC (1997) Quantum chemical and free energy simulation analysis of retinal conformational energetics. J Chem Inf Comput Sci 37:1018–1024

    CAS  Google Scholar 

  • Baudry J, Crouzy S, Roux B, Smith JC (1999) Simulation analysis of the retinal conformational equilibrium in dark-adapted bacteriorhodopsin. Biophys J 76:1909–1917

    CAS  PubMed  PubMed Central  Google Scholar 

  • Baudry J, Tajkhorshid E, Molnar F, Phillips J, Schulten K (2001) Molecular dynamics study of bacteriorhodopsin and the purple membrane. J Phys Chem B 105:905–918

    CAS  Google Scholar 

  • Bondar A-N, Knapp-Mohammady M, Suhai S, Fischer S, Smith JC (2011) Ground-state properties of the retinal molecule: from quantum mechanical to classical mechanical computations of retinal proteins. Theoret Chem Acc 130:1169–1183

    CAS  Google Scholar 

  • Bravaya K, Bochenkova A, Granovsky A, Nemukhin A (2007) An opsin shift in rhodopsin: retinal S0–S1 excitation in protein, in solution, and in the gas phase. J Am Chem Soc 129:13035–13042

    CAS  PubMed  Google Scholar 

  • Brown MF (1994) Modulation of rhodopsin function by properties of the membrane bilayer. Chem Phys Lipids 73:159–180

    CAS  PubMed  Google Scholar 

  • Brown MF (2012) Curvature forces in membrane lipid–protein interactions. Biochemistry 51:9782–9795

    CAS  PubMed  Google Scholar 

  • Brown MF (2017) Soft matter in lipid–protein interactions. Ann Rev Biophys 46:379–410

    CAS  Google Scholar 

  • Campomanes P, Neri M, Horta BA, Röhrig UF, Vanni S, Tavernelli I, Rothlisberger U (2014) Origin of the spectral shifts among the early intermediates of the rhodopsin photocycle. J Am Chem Soc 136:3842–3851

    CAS  PubMed  Google Scholar 

  • Caprasecca S, Jurinovich S, Viani L, Curutchet C, Mennucci B (2014) Geometry optimization in polarizable QM/MM models: the induced dipole formulation. J Chem Theory Comput 10:1588–1598

    CAS  PubMed  Google Scholar 

  • Chen J, Hundertmark D, Martínez TJ (2008) A unified theoretical framework for fluctuating-charge models in atom-space and in bond-space. J Chem Phys 129:214113

    PubMed  Google Scholar 

  • Chen H-F, Inoue K, Ono H, Abe-Yoshizumi R, Wada A, Kandori H (2018) Time-resolved FTIR study of light-driven sodium pump rhodopsins. Phys Chem Chem Phys 20:17694–17704

    CAS  PubMed  Google Scholar 

  • Choe H-W, Kim YJ, Park JH, Morizumi T, Pai EF, Krauss N, Hofmann KP, Scheerer P, Ernst OP (2011) Crystal structure of metarhodopsin II. Nature 471:651–655

    CAS  PubMed  Google Scholar 

  • Chothia C, Lesk AM (1986) The relation between the divergence of sequence and structure in proteins. EMBO J 5:823–826

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chung WC, Nanbu S, Ishida T (2012) QM/MM trajectory surface hopping approach to photoisomerization of rhodopsin and isorhodopsin: the origin of faster and more efficient isomerization for rhodopsin. J Phys Chem B 116:8009–8023

    CAS  PubMed  Google Scholar 

  • Chung LW, Sameera WMC, Ramozzi R, Page AJ, Hatanaka M, Petrova GP, Harris TV, Li X, Ke Z, Liu F, Li H-B, Ding L, Morokuma K (2015) The ONIOM method and its applications. Chem Rev 115:5678–5796

    CAS  PubMed  Google Scholar 

  • Cordomí A, Caltabiano G, Pardo L (2012) Membrane protein simulations using AMBER force field and Berger lipid parameters. J Chem Theory Comput 8:948–958

    PubMed  Google Scholar 

  • Cornell WD, Cieplak P, Bayly CI, Gould IR, Merz KM, Ferguson DM, Spellmeyer DC, Fox T, Caldwell JW, Kollman PA (1995) A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J Am Chem Soc 117:5179–5197

    CAS  Google Scholar 

  • Coto PB, Sinicropi A, De Vico L, Ferré N, Olivucci M (2006a) Characterization of the conical intersection of the visual pigment rhodopsin at the CASPT2//CASSCF/AMBER level of theory. Mol Phys 104:983–991

    CAS  Google Scholar 

  • Coto PB, Strambi A, Ferré N, Olivucci M (2006b) The color of rhodopsins at the ab initio multiconfigurational perturbation theory resolution. Proc Natl Acad Sci USA 103:17154–17159

    CAS  PubMed  PubMed Central  Google Scholar 

  • Coto PB, Strambi A, Olivucci M (2008) Effect of opsin on the shape of the potential energy surfaces at the conical intersection of the rhodopsin chromophore. Chem Phys 347:483–491

    CAS  Google Scholar 

  • Coutinho K, Georg H, Fonseca T, Ludwig V, Canuto S (2007) An efficient statistically converged average configuration for solvent effects. Chem Phys Lett 437:148–152

    CAS  Google Scholar 

  • Crouzy S, Baudry J, Smith JC, Roux B (1999) Efficient calculation of two-dimensional adiabatic and free energy maps: application to the isomerization of the C13–C14 and C15–N16 bonds in the retinal of bacteriorhodopsin. J Comput Chem 20:1644–1658

    CAS  Google Scholar 

  • Crozier PS, Stevens MJ, Forrest LR, Woolf TB (2003) Molecular dynamics simulation of dark-adapted rhodopsin in an explicit membrane bilayer: coupling between local retinal and larger scale conformational change. J Mol Biol 333:493–514

    CAS  PubMed  Google Scholar 

  • Curchod BF, Martínez TJ (2018) Ab initio nonadiabatic quantum molecular dynamics. Chem Rev 118:3305–3336

    CAS  PubMed  Google Scholar 

  • De Groot HJ, Smith SO, Courtin J, Van den Berg E, Winkel C, Lugtenburg J, Griffin RG, Herzfeld J (1990) Solid-state carbon-13 and nitrogen-15 NMR study of the low pH forms of bacteriorhodopsin. Biochemistry 29:6873–6883

    PubMed  Google Scholar 

  • Deupi X, Edwards P, Singhal A, Nickle B, Oprian D, Schertler G, Standfuss J (2012) Stabilized G protein binding site in the structure of constitutively active metarhodopsin-II. Proc Natl Acad Sci USA 109:119–124

    CAS  PubMed  Google Scholar 

  • Dickson CJ, Madej BD, Skjevik ÅA, Betz RM, Teigen K, Gould IR, Walker RC (2014) Lipid14: the Amber lipid force field. J Chem Theory Comput 10:865–879

    CAS  PubMed  PubMed Central  Google Scholar 

  • Doemer M, Maurer P, Campomanes P, Tavernelli I, Rothlisberger U (2013) Generalized QM/MM force matching approach applied to the 11-cis protonated Schiff base chromophore of rhodopsin. J Chem Theory Comput 10:412–422

    PubMed  Google Scholar 

  • Dolinsky TJ, Nielsen JE, McCammon JA, Baker NA (2004) PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations. Nucleic Acids Res 32:W665–W667

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dolinsky TJ, Czodrowski P, Li H, Nielsen JE, Jensen JH, Klebe G, Baker NA (2007) PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Res 35:W522–W525

    PubMed  PubMed Central  Google Scholar 

  • Dorn M, de Silva MB, Buriol LS, Lamb LC (2014) Three-dimensional protein structure prediction: methods and computational strategies. Comput Biol Chem 53:251–276

    CAS  Google Scholar 

  • Dror RO, Arlow DH, Borhani DW, Jensen MØ, Piana S, Shaw DE (2009) Identification of two distinct inactive conformations of the β 2-adrenergic receptor reconciles structural and biochemical observations. Proc Natl Acad Sci USA 106:4689–4694

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dror RO, Arlow DH, Maragakis P, Mildorf TJ, Pan AC, Xu H, Borhani DW, Shaw DE (2011) Activation mechanism of the β 2-adrenergic receptor. Proc Natl Acad Sci USA 108:18684–18689

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dror RO, Green HF, Valant C, Borhani DW, Valcourt JR, Pan AC, Arlow DH, Canals M, Lane JR, Rahmani R, Baell JB, Sexton PM, Christopoulos A, Shaw DE (2013) Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs. Nature 503:295–299

    CAS  PubMed  Google Scholar 

  • Dror RO, Mildorf TJ, Hilger D, Manglik A, Borhani DW, Arlow DH, Philippsen A, Villanueva N, Yang Z, Lerch MT, Hubbell WL, Kobilka BK, Sunahara RK, Shaw DE (2015) Structural basis for nucleotide exchange in heterotrimeric G proteins. Science 348:1361–1365

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ebejer J-P, Hill JR, Kelm S, Shi J, Deane CM (2013) Memoir: template-based structure prediction for membrane proteins. Nucleic Acids Res 41:W379–W383

    PubMed  PubMed Central  Google Scholar 

  • El-Khoury PZ, Tarnovsky AN, Schapiro I, Ryazantsev MN, Olivucci M (2009) Structure of the photochemical reaction path populated via promotion of CF2I2 into its first excited state. J Phys Chem A 113:10767–10771

    CAS  PubMed  Google Scholar 

  • Elstner M (2006) The SCC-DFTB method and its application to biological systems. Theoret Chem Acc 116:316–325

    CAS  Google Scholar 

  • Elstner M, Frauenheim T, Suhai S (2003) An approximate DFT method for QM/MM simulations of biological structures and processes. J Mol Struct (Theochem) 632:29–41

    CAS  Google Scholar 

  • Eswar N, Webb B, Marti-Renom MA, Madhusudhan MS, Eramian D, Shen M-y, Pieper U, Sali A (2006) Comparative protein structure modeling using Modeller. Curr Protoc Bioinf 15:5.6.1–5.6.30

    Google Scholar 

  • Feig M (2008) Implicit membrane models for membrane protein simulation. Methods Mol Biol 443:181–196

    CAS  PubMed  Google Scholar 

  • Feller SE, Gawrisch K, Woolf TB (2003) Rhodopsin exhibits a preference for solvation by polyunsaturated docosohexaenoic acid. J Am Chem Soc 125:4434–4435

    CAS  PubMed  Google Scholar 

  • Feng J, Brown MF, Mertz B (2015) Retinal flip in rhodopsin activation? Biophys J 108:2767–2770

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrand M, Zaccai G, Nina M, Smith J, Etchebest C, Roux B (1993) Structure and dynamics of bacteriorhodopsin: comparison of simulation and experiment. FEBS Lett 327:256–260

    CAS  PubMed  Google Scholar 

  • Field MJ, Bash PA, Karplus M (1990) A combined quantum mechanical and molecular mechanical potential for molecular dynamics simulations. J Comput Chem 11:700–733

    CAS  Google Scholar 

  • Finley J, Malmqvist P-Å, Roos BO, Serrano-Andrés L (1998) The multi-state CASPT2 method. Chem Phys Lett 288:299–306

    CAS  Google Scholar 

  • Fracchia F, Del Frate G, Mancini G, Rocchia W, Barone V (2017) Force field parametrization of metal ions from statistical learning techniques. J Chem Theory Comput 14:255–273

    PubMed  PubMed Central  Google Scholar 

  • Frähmcke JS, Wanko M, Phatak P, Mroginski MA, Elstner M (2010) The protonation state of Glu181 in rhodopsin revisited: interpretation of experimental data on the basis of QM/MM calculations. J Phys Chem B 114:11338–11352

    PubMed  Google Scholar 

  • Frähmcke JS, Wanko M, Elstner M (2012) Building a model of the blue cone pigment based on the wild type rhodopsin structure with QM/MM methods. J Phys Chem B 116:3313–3321

    PubMed  Google Scholar 

  • Frutos LM, Andruniów T, Santoro F, Ferré N, Olivucci M (2007) Tracking the excited-state time evolution of the visual pigment with multiconfigurational quantum chemistry. Proc Natl Acad Sci USA 104:7764–7769

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fujimoto K, Hasegawa J-y, Hayashi S, Kato S, Nakatsuji H (2005) Mechanism of color tuning in retinal protein: SAC-CI and QM/MM study. Chem Phys Lett 414:239–242

    CAS  Google Scholar 

  • Fujimoto K, Hasegawa J-y, Hayashi S, Nakatsuji H (2006) On the color-tuning mechanism of Human-Blue visual pigment: SAC-CI and QM/MM study. Chem Phys Lett 432:252–256

    CAS  Google Scholar 

  • Fujimoto KJ, Asai K, Hasegawa J-y (2010) Theoretical study of the opsin shift of deprotonated retinal Schiff base in the M state of bacteriorhodopsin. Phys Chem Chem Phys 12:13107–13116

    CAS  PubMed  Google Scholar 

  • Galván IF, Sánchez M, Martín M, Olivares del Valle F, Aguilar M (2003) Geometry optimization of molecules in solution: joint use of the mean field approximation and the free-energy gradient method. J Chem Phys 118:255–263

    Google Scholar 

  • Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity—a rapid access to atomic charges. Tetrahedron 36:3219–3228

    CAS  Google Scholar 

  • Gaus M, Cui Q, Elstner M (2011) DFTB3: extension of the self-consistent-charge density-functional tight-binding method (SCC-DFTB). J Chem Theory Comput 7:931–948

    CAS  Google Scholar 

  • Gellini C, Lüttenberg B, Sydor J, Engelhard M, Hildebrandt P (2000) Resonance Raman spectroscopy of sensory rhodopsin II from Natronobacterium pharaonis. FEBS Lett 472:263–266

    CAS  PubMed  Google Scholar 

  • González A, Perez-Acle T, Pardo L, Deupi X (2011) Molecular basis of ligand dissociation in β-adrenergic receptors. PLoS ONE 6:e23815

    PubMed  PubMed Central  Google Scholar 

  • González-Luque R, Garavelli M, Bernardi F, Merchán M, Robb MA, Olivucci M (2000) Computational evidence in favor of a two-state, two-mode model of the retinal chromophore photoisomerization. Proc Natl Acad Sci USA 97:9379–9384

    PubMed  PubMed Central  Google Scholar 

  • Govorunova EG, Cunha SR, Sineshchekov OA, Spudich JL (2016) Anion channelrhodopsins for inhibitory cardiac optogenetics. Sci Rep 6:33530

    CAS  PubMed  PubMed Central  Google Scholar 

  • Govorunova EG, Sineshchekov OA, Li H, Spudich JL (2017) Microbial rhodopsins: diversity, mechanisms, and optogenetic applications. Annu Rev Biochem 86:845–872

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gozem S, Luk HL, Schapiro I, Olivucci M (2017) Theory and simulation of the ultrafast double-bond isomerization of biological chromophores. Chem Rev 117:13502–13565

    CAS  PubMed  Google Scholar 

  • Grossfield A (2008) Implicit modeling of membranes. Curr Top Membr 60:131–157

    CAS  Google Scholar 

  • Grossfield A (2011) Recent progress in the study of G protein-coupled receptors with molecular dynamics computer simulations. Biochim Biophys Acta 1808:1868–1878

    CAS  PubMed  Google Scholar 

  • Grossfield A, Feller SE, Pitman MC (2006a) Contribution of omega-3 fatty acids to the thermodynamics of membrane protein solvation. J Phys Chem B 110:8907–8909

    CAS  PubMed  Google Scholar 

  • Grossfield A, Feller SE, Pitman MC (2006b) A role for direct interactions in the modulation of rhodopsin by ω-3 polyunsaturated lipids. Proc Natl Acad Sci USA 103:4888–4893

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guo Y, Beyle FE, Bold BM, Watanabe HC, Koslowski A, Thiel W, Hegemann P, Marazzi M, Elstner M (2016) Active site structure and absorption spectrum of channelrhodopsin-2 wild-type and C128T mutant. Chem Sci 7:3879–3891

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gushchin I, Gordeliy V, Grudinin S (2013) Two distinct states of the HAMP domain from sensory rhodopsin transducer observed in unbiased molecular dynamics simulations. PLoS ONE 8:e66917

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gushchin I, Shevchenko V, Polovinkin V, Kovalev K, Alekseev A, Round E, Borshchevskiy V, Balandin T, Popov A, Gensch T, Fahlke C, Baumann C, Willbold D, Büldt G, Bamberg E, Gordelly V (2015) Crystal structure of a light-driven sodium pump. Nat Struct Mol Biol 22:390–395

    CAS  PubMed  Google Scholar 

  • Gutiérrez-de-Terán H, Massink A, Rodríguez D, Liu W, Han GW, Joseph JS, Katritch I, Heitman LH, Xia L, IJzerman AP, Chereƶov V, Katritch V, Stevens RC (2013) The role of a sodium ion binding site in the allosteric modulation of the A2A adenosine G protein-coupled receptor. Structure 21:2175–2185

    PubMed  Google Scholar 

  • Hall KF, Vreven T, Frisch MJ, Bearpark MJ (2008) Three-layer ONIOM studies of the dark state of rhodopsin: the protonation state of Glu181. J Mol Biol 383:106–121

    CAS  PubMed  Google Scholar 

  • Hamanaka T, Mitsui T, Ashida T, Kakudo M (1972) The crystal structure of all-trans retinal1. Acta Crystallogr B 28:214–222

    CAS  Google Scholar 

  • Hansen N, Van Gunsteren WF (2014) Practical aspects of free-energy calculations: a review. J Chem Theory Comput 10:2632–2647

    CAS  PubMed  Google Scholar 

  • Harbison GS, Roberts JE, Herzfeld J, Griffin RG (1988) Solid-state NMR detection of proton exchange between the bacteriorhodopsin Schiff base and bulk water. J Am Chem Soc 110:7221–7223

    CAS  Google Scholar 

  • Hayashi S, Tajkhorshid E, Schulten K (2002) Structural changes during the formation of early intermediates in the bacteriorhodopsin photocycle. Biophys J 83:1281–1297

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hein M, Wegener AA, Engelhard M, Siebert F (2003) Time-resolved FTIR studies of sensory rhodopsin II (NpSRII) from Natronobacterium pharaonis: implications for proton transport and receptor activation. Biophys J 84:1208–1217

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hénin J, Maigret B, Tarek M, Escrieut C, Fourmy D, Chipot C (2006) Probing a model of a GPCR/ligand complex in an explicit membrane environment: the human cholecystokinin-1 receptor. Biophys J 90:1232–1240

    PubMed  Google Scholar 

  • Hill JR, Deane CM (2012) MP-T: improving membrane protein alignment for structure prediction. Bioinformatics 29:54–61

    PubMed  Google Scholar 

  • Hillebrecht JR, Galan J, Rangarajan R, Ramos L, McCleary K, Ward DE, Stuart JA, Birge RR (2006) Structure, function, and wavelength selection in blue-absorbing proteorhodopsin. Biochemistry 45:1579–1590

    CAS  PubMed  Google Scholar 

  • Hochbaum DR, Zhao Y, Farhi SL, Klapoetke N, Werley CA, Kapoor V, Zou P, Kralj JM, Maclaurin D, Smedemark-Margulies N (2014) All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nat Methods 11:825–833

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann M, Wanko M, Strodel P, König PH, Frauenheim T, Schulten K, Thiel W, Tajkhorshid E, Elstner M (2006) Color tuning in rhodopsins: the mechanism for the spectral shift between bacteriorhodopsin and sensory rhodopsin II. J Am Chem Soc 128:10808–10818

    CAS  PubMed  Google Scholar 

  • Horn JN, Kao T-C, Grossfield A (2014) Coarse-grained molecular dynamics provides insight into the interactions of lipids and cholesterol with rhodopsin. Adv Exp Med Biol 796:75–94

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hornak V, Ahuja S, Eilers M, Goncalves JA, Sheves M, Reeves PJ, Smith SO (2010) Light activation of rhodopsin: insights from molecular dynamics simulations guided by solid-state NMR distance restraints. J Mol Biol 396:510–527

    CAS  PubMed  Google Scholar 

  • Huang W, Manglik A, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, Kato HE, Livingston KE, Thorsen TS, Kling RC, Granier S, Gmeiner P, Husbands SM, Traynor JR, Weiss WI, Steyaert J, Dror RO, Kobilka BK (2015) Structural insights into µ-opioid receptor activation. Nature 524:315–321

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huber T, Sakmar TP (2008) Rhodopsin’s active state is frozen like a DEER in the headlights. Proc Natl Acad Sci USA 105:7343–7344

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huber T, Botelho AV, Beyer K, Brown MF (2004) Membrane model for the G-protein-coupled receptor rhodopsin: hydrophobic interface and dynamical structure. Biophys J 86:2078–2100

    CAS  PubMed  PubMed Central  Google Scholar 

  • Im W, Feig M, Brooks CL III (2003) An implicit membrane generalized Born theory for the study of structure, stability, and interactions of membrane proteins. Biophys J 85:2900–2918

    CAS  PubMed  PubMed Central  Google Scholar 

  • Isralewitz B, Izrailev S, Schulten K (1997) Binding pathway of retinal to bacterio-opsin: a prediction by molecular dynamics simulations. Biophys J 73:2972–2979

    CAS  PubMed  PubMed Central  Google Scholar 

  • Izvekov S, Voth GA (2005) A multiscale coarse-graining method for biomolecular systems. J Phys Chem B 109:2469–2473

    CAS  PubMed  Google Scholar 

  • Jämbeck JP, Lyubartsev AP (2012) An extension and further validation of an all-atomistic force field for biological membranes. J Chem Theory Comput 8:2938–2948

    PubMed  Google Scholar 

  • Jardón-Valadez E, Bondar A-N, Tobias DJ (2010) Coupling of retinal, protein, and water dynamics in squid rhodopsin. Biophys J 99:2200–2207

    PubMed  PubMed Central  Google Scholar 

  • Jarzynski C (1997) Equilibrium free-energy differences from nonequilibrium measurements: a master-equation approach. Phys Rev E 56:5018

    CAS  Google Scholar 

  • Jensen MR, Zweckstetter M, Huang J-r, Blackledge M (2014) Exploring free-energy landscapes of intrinsically disordered proteins at atomic resolution using NMR spectroscopy. Chem Rev 114:6632–6660

    CAS  PubMed  Google Scholar 

  • Johnston JM, Wang H, Provasi D, Filizola M (2012) Assessing the relative stability of dimer interfaces in G protein-coupled receptors. PLoS Comput Biol 8:e1002649

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kaminski GA, Friesner RA, Tirado-Rives J, Jorgensen WL (2001) Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J Phys Chem B 105:6474–6487

    CAS  Google Scholar 

  • Kästner J (2011) Umbrella sampling. Wiley Interdiscip Rev 1:932–942

    Google Scholar 

  • Kaszuba K, Róg T, Bryl K, Vattulainen I, Karttunen M (2010) Molecular dynamics simulations reveal fundamental role of water as factor determining affinity of binding of β-blocker nebivolol to β 2-adrenergic receptor. J Phys Chem B 114:8374–8386

    CAS  PubMed  Google Scholar 

  • Kaufmann KW, Lemmon GH, DeLuca SL, Sheehan JH, Meiler J (2010) Practically useful: what the Rosetta protein modeling suite can do for you. Biochemistry 49:2987–2998

    CAS  PubMed  Google Scholar 

  • Kazmin R, Rose A, Szczepek M, Elgeti M, Ritter E, Piechnick R, Hofmann KP, Scheerer P, Hildebrand PW, Bartl FJ (2015) The activation pathway of human rhodopsin in comparison to bovine rhodopsin. J Biol Chem 290:20117–201127

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kelm S, Shi J, Deane CM (2010) MEDELLER: homology-based coordinate generation for membrane proteins. Bioinformatics 26:2833–2840

    CAS  PubMed  PubMed Central  Google Scholar 

  • Khan FI, Wei D-Q, Gu K-R, Hassan MI, Tabrez S (2016) Current updates on computer aided protein modeling and designing. Int J Biol Macromol 85:48–62

    CAS  PubMed  Google Scholar 

  • Khandogin J, Brooks CL (2005) Constant pH molecular dynamics with proton tautomerism. Biophys J 89:141–157

    CAS  PubMed  PubMed Central  Google Scholar 

  • Khelashvili G, Albornoz PBC, Johner N, Mondal S, Caffrey M, Weinstein H (2012) Why GPCRs behave differently in cubic and lamellar lipidic mesophases. J Am Chem Soc 134:15858–15868

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kholmurodov KT, Fel’dman T, Ostrovskii M (2007) Molecular dynamics of rhodopsin and free opsin: computer simulation. Neurosci Behav Physiol 37:161–174

    CAS  PubMed  Google Scholar 

  • Khrenova MG, Bochenkova AV, Nemukhin AV (2010) Modeling reaction routes from rhodopsin to bathorhodopsin. Proteins 78:614–622

    CAS  PubMed  Google Scholar 

  • Kilambi KP, Gray JJ (2012) Rapid calculation of protein pK a values using Rosetta. Biophys J 103:587–595

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klauda JB, Venable RM, Freites JA, O’Connor JW, Tobias DJ, Mondragon-Ramirez C, Vorobyov I, MacKerell AD Jr, Pastor RW (2010) Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B 114:7830–7843

    CAS  PubMed  PubMed Central  Google Scholar 

  • Krebs A, Edwards PC, Villa C, Li J, Schertler GFX (2003) The three-dimensional structure of bovine rhodopsin determined by electron cryomicroscopy. J Biol Chem 278:50217–50225

    CAS  PubMed  Google Scholar 

  • Kukura P, McCamant DW, Yoon S, Wandschneider DB, Mathies RA (2005) Structural observation of the primary isomerization in vision with femtosecond-stimulated Raman. Science 310:1006–1009

    CAS  PubMed  Google Scholar 

  • Kumar S, Rosenberg JM, Bouzida D, Swendsen RH, Kollman PA (1992) The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method. J Comput Chem 13:1011–1021

    CAS  Google Scholar 

  • Laio A, Gervasio FL (2008) Metadynamics: a method to simulate rare events and reconstruct the free energy in biophysics, chemistry and material science. Rep Prog Phys 71:126601

    Google Scholar 

  • Laio A, Parrinello M (2002) Escaping free-energy minima. Proc Natl Acad Sci USA 99:12562–12566

    CAS  PubMed  PubMed Central  Google Scholar 

  • Latorraca NR, Venkatakrishnan A, Dror RO (2017) GPCR dynamics: structures in motion. Chem Rev 117:139–155

    CAS  PubMed  Google Scholar 

  • Latorraca NR, Wang JK, Bauer B, Townshend RJ, Hollingsworth SA, Olivieri JE, Xu HE, Sommer ME, Dror RO (2018) Molecular mechanism of GPCR-mediated arrestin activation. Nature 557:452–456

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lau P-W, Grossfield A, Feller SE, Pitman MC, Brown MF (2007) Dynamic structure of retinylidene ligand of rhodopsin probed by molecular simulations. J Mol Biol 372:906–917

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee J, Freddolino PL, Zhang Y (2017) Ab initio protein structure prediction. In: Daniel JR (ed) From Protein Structure to Function with Bioinformatics. Springer, Berlin, pp 3–35

    Google Scholar 

  • Leguèbe M, Nguyen C, Capece L, Hoang Z, Giorgetti A, Carloni P (2012) Hybrid molecular mechanics/coarse-grained simulations for structural prediction of G-protein coupled receptor/ligand complexes. PLoS ONE 7:e47332

    PubMed  PubMed Central  Google Scholar 

  • Leioatts N, Mertz B, Martínez-Mayorga K, Romo TD, Pitman MC, Feller SE, Grossfield A, Brown MF (2014) Retinal ligand mobility explains internal hydration and reconciles active rhodopsin structures. Biochemistry 53:376–385

    CAS  PubMed  Google Scholar 

  • Lemaître V, Yeagle P, Watts A (2005) Molecular dynamics simulations of retinal in rhodopsin: from the dark-adapted state towards lumirhodopsin. Biochemistry 44:12667–12680

    PubMed  Google Scholar 

  • Lenselink EB, Louvel J, Forti AF, van Veldhoven JPD, de Vries H, Mulder-Krieger T, McRobb FM, Negri A, Goose J, Abel R, van Vlijmen HWT, Wang L, Harder E, Sherman W, IJƶerman AP, Beuming T (2016) Predicting binding affinities for GPCR ligands using free-energy perturbation. ACS Omega 1:293–304

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leonard AN, Pastor RW, Klauda JB (2018) Parameterization of the CHARMM all-atom force field for ether lipids and model linear ethers. J Phys Chem B 122:6744–6754

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Chung LW, Morokuma K (2011) Photodynamics of all-trans retinal protonated Schiff base in bacteriorhodopsin and methanol solution. J Chem Theory Comput 7:2694–2698

    CAS  PubMed  Google Scholar 

  • Lin H, Truhlar DG (2007) QM/MM: what have we learned, where are we, and where do we go from here? Theoret Chem Acc 117:185–199

    CAS  Google Scholar 

  • Lindorff-Larsen K, Piana S, Palmo K, Maragakis P, Klepeis JL, Dror RO, Shaw DE (2010) Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins 78:1950–1958

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lischka H, Dallos M, Shepard R (2002) Analytic MRCI gradient for excited states: formalism and application to the n-π∗ valence-and n-(3s, 3p) Rydberg states of formaldehyde. Mol Phys 100:1647–1658

    CAS  Google Scholar 

  • Mackerell AD Jr, Feig M, Brooks CL III (2004) Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J Comput Chem 25:1400–1415

    CAS  PubMed  Google Scholar 

  • Maclaurin D, Venkatachalam V, Lee H, Cohen AE (2013) Mechanism of voltage-sensitive fluorescence in a microbial rhodopsin. Proc Natl Acad Sci USA 110:5939–5944

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marchiori A, Capece L, Giorgetti A, Gasparini P, Behrens M, Carloni P, Meyerhof W (2013) Coarse-grained/molecular mechanics of the TAS2R38 bitter taste receptor: experimentally-validated detailed structural prediction of agonist binding. PLoS ONE 8:e64675

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marrink SJ, De Vries AH, Mark AE (2004) Coarse grained model for semiquantitative lipid simulations. J Phys Chem B 108:750–760

    CAS  Google Scholar 

  • Marrink SJ, Risselada HJ, Yefimov S, Tieleman DP, De Vries AH (2007) The MARTINI force field: coarse grained model for biomolecular simulations. J Phys Chem B 111:7812–7824

    CAS  PubMed  Google Scholar 

  • Martínez-Mayorga K, Pitman MC, Grossfield A, Feller SE, Brown MF (2006) Retinal counterion switch mechanism in vision evaluated by molecular simulations. J Am Chem Soc 128:16502–16503

    PubMed  Google Scholar 

  • Melaccio F, Ferré N, Olivucci M (2012) Quantum chemical modeling of rhodopsin mutants displaying switchable colors. Phys Chem Chem Phys 14:12485–12495

    CAS  PubMed  Google Scholar 

  • Meral D, Provasi D, Filizola M (2018) An efficient strategy to estimate thermodynamics and kinetics of G protein-coupled receptor activation using metadynamics and maximum caliber. J Chem Phys 149:224101

    PubMed  PubMed Central  Google Scholar 

  • Mertz B, Lu M, Brown MF, Feller SE (2011) Steric and electronic influences on the torsional energy landscape of retinal. Biophys J 101:L17–L19

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mertz B, Struts AV, Feller SE, Brown MF (2012) Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation. Biochem Biophys Acta 1818:241–251

    CAS  PubMed  Google Scholar 

  • Metropolis N, Ulam S (1949) The Monte Carlo method. J Am Stat Assoc 44:335–341

    CAS  PubMed  Google Scholar 

  • Miao Y, Caliman AD, McCammon JA (2015) Allosteric effects of sodium ion binding on activation of the M3 muscarinic G-protein-coupled receptor. Biophys J 108:1796–1806

    CAS  PubMed  PubMed Central  Google Scholar 

  • Monticelli L, Kandasamy SK, Periole X, Larson RG, Tieleman DP, Marrink S-J (2008) The MARTINI coarse-grained force field: extension to proteins. J Chem Theory Comput 4:819–834

    CAS  PubMed  Google Scholar 

  • Moradi M, Babin V, Sagui C, Roland C (2013) Recipes for free energy calculations in biomolecular systems. Methods Mol Biol 924:313–337

    CAS  PubMed  Google Scholar 

  • Mori T, Miyashita N, Im W, Feig M, Sugita Y (2016) Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms. Biochim Biophys Acta 1858:1635–1651

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morozenko A, Stuchebrukhov A (2016) Dowser++, a new method of hydrating protein structures. Proteins 84:1347–1357

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morozenko A, Leontyev I, Stuchebrukhov A (2014) Dipole moment and binding energy of water in proteins from crystallographic analysis. J Chem Theory Comput 10:4618–4623

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nielsen IB, Lammich L, Andersen LH (2006) S1 and S2 excited states of gas-phase Schiff-base retinal chromophores. Phys Rev Lett 96:018304

    CAS  PubMed  Google Scholar 

  • Nikolaev DM, Emelyanov A, Boitsov VM, Panov MS, Ryazantsev MN (2017) A voltage-dependent fluorescent indicator for optogenetic applications, archaerhodopsin-3: structure and optical properties from in silico modeling. F1000Research 6:33

    PubMed  PubMed Central  Google Scholar 

  • Nikolaev DM, Shtyrov AA, Panov MS, Jamal A, Chakchir OB, Kochemirovsky VA, Olivucci M, Ryazantsev MN (2018) A comparative study of modern homology modeling algorithms for rhodopsin structure prediction. ACS Omega 3:7555–7566

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nikolaev DM, Osipov DE, Strashkov DM, Vyazmin SY, Akulov VE, Kravtcov DV, Chakchir OB, Panov MS, Ryazantsev MN (2019a) Molecular mechanisms of adaptation to the habitat depth in visual pigments of A. subulata and L. forbesi squids: on the role of the S270F substitution. J Integr OMICS 9:44–50

    Google Scholar 

  • Nikolaev DM, Panov MS, Shtyrov AA, Boitsov VM, Vyazmin SY, Chakchir OB, Yakovlev IP, Ryazantsev MN (2019b) Perspective tools for optogenetics and photopharmacology: from design to implementation. In: Yamanouchi K, Tunik S, Makarov V (eds) Progress in Photon Science. Springer, Berlin, pp 139–172

    Google Scholar 

  • Nina M, Roux B, Smith JC (1995) Functional interactions in bacteriorhodopsin: a theoretical analysis of retinal hydrogen bonding with water. Biophys J 68:25–39

    CAS  PubMed  PubMed Central  Google Scholar 

  • Noid W (2013) Systematic methods for structurally consistent coarse-grained models. Methods Mol Biol 924:487–531

    CAS  PubMed  Google Scholar 

  • Nygaard R, Zou Y, Dror RO, Mildorf TJ, Arlow DH, Manglik A, Pan AC, Liu CW, Fung JJ, Bokoch MP, Thian FS, Kobilka TS, Shaw DE, Mueller L, Prosser RS, Kobilka BK (2013) The dynamic process of β 2-adrenergic receptor activation. Cell 152:532–542

    CAS  PubMed  PubMed Central  Google Scholar 

  • Okuyama-Yoshida N, Kataoka K, Nagaoka M, Yamabe T (2000) Structure optimization via free energy gradient method: application to glycine zwitterion in aqueous solution. J Chem Phys 113:3519–3524

    CAS  Google Scholar 

  • Olausson BE, Grossfield A, Pitman MC, Brown MF, Feller SE, Vogel A (2012) Molecular dynamics simulations reveal specific interactions of post-translational palmitoyl modifications with rhodopsin in membranes. J Am Chem Soc 134:4324–4331

    CAS  PubMed  PubMed Central  Google Scholar 

  • Olsson MHM, Søndergaard CR, Rostkowski M, Jensen JH (2011) PROPKA3: consistent treatment of internal and surface residues in empirical pK a predictions. J Chem Theory Comput 7:525–537

    CAS  PubMed  Google Scholar 

  • Oostenbrink C, Villa A, Mark AE, Van Gunsteren WF (2004) A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J Comput Chem 25:1656–1676

    CAS  PubMed  Google Scholar 

  • Orozco-Gonzalez Y, Manathunga M, Marin MdC, Agathangelou D, Jung KH, Melaccio F, Ferré N, Haacke S, Coutinho K, Canuto S, Olivucci M (2017) An average solvent electrostatic configuration protocol for QM/MM free energy optimization: implementation and application to rhodopsin systems. J Chem Theory Comput 13:6391–6404

    CAS  PubMed  Google Scholar 

  • Pastor R, MacKerell AD Jr (2011) Development of the CHARMM force field for lipids. J Phys Chem Lett 2:1526–1532

    CAS  PubMed  PubMed Central  Google Scholar 

  • Patel AB, Crocker E, Eilers M, Hirshfeld A, Sheves M, Smith SO (2004) Coupling of retinal isomerization to the activation of rhodopsin. Proc Natl Acad Sci USA 101:10048–10053

    CAS  PubMed  PubMed Central  Google Scholar 

  • Perera SM, Chawla U, Shrestha UR, Bhowmik D, Struts AV, Qian S, Chu X-Q, Brown MF (2018) Small-angle neutron scattering reveals energy landscape for rhodopsin photoactivation. J Phys Chem Lett 9:7064–7071

    CAS  PubMed  Google Scholar 

  • Periole X (2016) Interplay of G protein-coupled receptors with the membrane: insights from supra-atomic coarse grain molecular dynamics simulations. Chem Rev 117:156–185

    PubMed  Google Scholar 

  • Periole X, Huber T, Marrink S-J, Sakmar TP (2007) G protein-coupled receptors self-assemble in dynamics simulations of model bilayers. J Am Chem Soc 129:10126–10132

    CAS  PubMed  Google Scholar 

  • Periole X, Knepp AM, Sakmar TP, Marrink SJ, Huber T (2012) Structural determinants of the supramolecular organization of G protein-coupled receptors in bilayers. J Am Chem Soc 134:10959–10965

    CAS  PubMed  PubMed Central  Google Scholar 

  • Provasi D, Filizola M (2010) Putative active states of a prototypic G-protein-coupled receptor from biased molecular dynamics. Biophys J 98:2347–2355

    CAS  PubMed  PubMed Central  Google Scholar 

  • Provasi D, Palczewski K, Filizola M (2009) Exploring the thermodynamics of activation pathways of bovine rhodopsin with fast molecular dynamics simulations. Biophys J 96:679a

    Google Scholar 

  • Raiteri P, Laio A, Gervasio FL, Micheletti C, Parrinello M (2006) Efficient reconstruction of complex free energy landscapes by multiple walkers metadynamics. J Phys Chem B 110:3533–3539

    CAS  PubMed  Google Scholar 

  • Rajamani R, Gao J (2002) Combined QM/MM study of the opsin shift in bacteriorhodopsin. J Comput Chem 23:96–105

    CAS  PubMed  Google Scholar 

  • Richards R, Dempski RE (2017) Adjacent channelrhodopsin-2 residues within transmembranes 2 and 7 regulate cation selectivity and distribution of the two open states. J Biol Chem 292:7314–7326

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rinaldi S, Melaccio F, Gozem S, Fanelli F, Olivucci M (2014) Comparison of the isomerization mechanisms of human melanopsin and invertebrate and vertebrate rhodopsins. Proc Natl Acad Sci USA 111:1714–1719

    CAS  PubMed  PubMed Central  Google Scholar 

  • Romo TD, Grossfield A, Pitman MC (2010) Concerted interconversion between ionic lock substates of the β 2 adrenergic receptor revealed by microsecond timescale molecular dynamics. Biophys J 98:76–84

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ross GA, Morris GM, Biggin PC (2012) Rapid and accurate prediction and scoring of water molecules in protein binding sites. PLoS ONE 7:e32036

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rostkowski M, Olsson MHM, Søndergaard CR, Jensen JH (2011) Graphical analysis of pH-dependent properties of proteins predicted using PROPKA. BMC Struct Biol 11:6

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rotov AY, Astakhova L, Sitnikova V, Evdokimov A, Boitsov V, Dubina M, Ryazantsev M, Firsov M (2018) New experimental models of retinal degeneration for screening molecular photochromic ion channel blockers. Acta Nat 10:75–84

    Google Scholar 

  • Roux B, Nina M, Pomès R, Smith JC (1996) Thermodynamic stability of water molecules in the bacteriorhodopsin proton channel: a molecular dynamics free energy perturbation study. Biophys J 71:670–681

    CAS  PubMed  PubMed Central  Google Scholar 

  • Roy A, Kucukural A, Zhang Y (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 5:725–738

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ryazantsev MN, Altun A, Morokuma K (2012) Color tuning in rhodopsins: the origin of the spectral shift between the chloride-bound and anion-free forms of halorhodopsin. J Am Chem Soc 134:5520–5523

    CAS  PubMed  PubMed Central  Google Scholar 

  • Saam J, Tajkhorshid E, Hayashi S, Schulten K (2002) Molecular dynamics investigation of primary photoinduced events in the activation of rhodopsin. Biophys J 83:3097–3112

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sahoo BR, Genjo T, Maharana KC, Ramamoorthy A (2019) Self-assembly of polymer-encased lipid nanodiscs and membrane protein reconstitution. J Phys Chem B 123:4562–4570

    CAS  PubMed  Google Scholar 

  • Saint Clair EC, Ogren JI, Mamaev S, Kralj JM, Rothschild KJ (2012a) Conformational changes in the archaerhodopsin-3 proton pump: detection of conserved strongly hydrogen bonded water networks. J Biol Phys 38:153–168

    CAS  Google Scholar 

  • Saint Clair EC, Ogren JI, Mamaev S, Russano D, Kralj JM, Rothschild KJ (2012b) Near-IR resonance Raman spectroscopy of archaerhodopsin 3: effects of transmembrane potential. J Phys Chem B 116:14592–14601

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sakmar TP, Periole X, Huber T (2017) Probing self-assembly of G protein-coupled receptor oligomers in membranes using molecular dynamics modeling and experimental approaches. In: Herrick-Davis K, Milligan G, Di Giovanni G (eds) G-Protein-Coupled Receptor Dimers. Humana Press, Cham, pp 385–414

    Google Scholar 

  • Salamon Z, Brown MF, Tollin G (1999) Plasmon resonance spectroscopy: probing molecular interactions within membranes. Trends Biochem Sci 24:213–219

    CAS  PubMed  Google Scholar 

  • Salas-Estrada LA, Leioatts N, Romo TD, Grossfield A (2018) Lipids alter rhodopsin function via ligand-like and solvent-like interactions. Biophys J 114:355–367

    CAS  PubMed  PubMed Central  Google Scholar 

  • Saleh N, Ibrahim P, Saladino G, Gervasio FL, Clark T (2017) An efficient metadynamics-based protocol to model the binding affinity and the transition state ensemble of G-protein-coupled receptor ligands. J Chem Inf Model 57:1210–1217

    CAS  PubMed  Google Scholar 

  • Saunders MG, Voth GA (2013) Coarse-graining methods for computational biology. Ann Rev Biophys 42:73–93

    CAS  Google Scholar 

  • Schaefer P, Riccardi D, Cui Q (2005) Reliable treatment of electrostatics in combined QM/MM simulation of macromolecules. J Chem Phys 123:014905

    PubMed  Google Scholar 

  • Schapiro I, Weingart O, Buss V (2008) Bicycle-pedal isomerization in a rhodopsin chromophore model. J Am Chem Soc 131:16–17

    Google Scholar 

  • Schapiro I, Ryazantsev MN, Frutos LM, Ferré N, Lindh R, Olivucci M (2011) The ultrafast photoisomerizations of rhodopsin and bathorhodopsin are modulated by bond length alternation and HOOP driven electronic effects. J Am Chem Soc 133:3354–3364

    CAS  PubMed  Google Scholar 

  • Schmidt TH, Kandt C (2012) LAMBADA and InflateGRO2: efficient membrane alignment and insertion of membrane proteins for molecular dynamics simulations. J Chem Inf Model 52:2657–2669

    CAS  PubMed  Google Scholar 

  • Schnedermann C, Yang X, Liebel M, Spillane K, Lugtenburg J, Fernández I, Valentini A, Schapiro I, Olivucci M, Kukura P, Mathies RA (2018) Evidence for a vibrational phase-dependent isotope effect on the photochemistry of vision. Nat Chem 10:449–455

    CAS  PubMed  Google Scholar 

  • Schoenlein RW, Peteanu LA, Mathies RA, Shank CV (1991) The first step in vision: femtosecond isomerization of rhodopsin. Science 254:412–415

    CAS  PubMed  Google Scholar 

  • Scott KA, Bond PJ, Ivetac A, Chetwynd AP, Khalid S, Sansom MS (2008) Coarse-grained MD simulations of membrane protein-bilayer self-assembly. Structure 16:621–630

    CAS  PubMed  Google Scholar 

  • Senn HM, Thiel W (2009) QM/MM methods for biomolecular systems. Angew Chem Int Ed 48:1198–1229

    CAS  Google Scholar 

  • Shirts MR, Mobley DL (2013) An introduction to best practices in free energy calculations. Methods Mol Biol 924:271–311

    CAS  PubMed  Google Scholar 

  • Shrestha UR, Perera SM, Bhowmik D, Chawla U, Mamontov E, Brown MF, Chu X-Q (2016) Quasi-elastic neutron scattering reveals ligand-induced protein dynamics of a G-protein-coupled receptor. J Phys Chem Lett 7:4130–4136

    CAS  PubMed  PubMed Central  Google Scholar 

  • Simonson T, Carlsson J, Case DA (2004) Proton binding to proteins: pK a calculations with explicit and implicit solvent models. J Am Chem Soc 126:4167–4180

    CAS  PubMed  Google Scholar 

  • Smith SO (2010) Structure and activation of the visual pigment rhodopsin. Ann Rev Biophys 39:309–328

    CAS  Google Scholar 

  • Söderhjelm P, Husberg C, Strambi A, Olivucci M, Ryde U (2009) Protein influence on electronic spectra modeled by multipoles and polarizabilities. J Chem Theory Comput 5:649–658

    PubMed  Google Scholar 

  • Söding J (2004) Protein homology detection by HMM–HMM comparison. Bioinformatics 21:951–960

    PubMed  Google Scholar 

  • Song Y, DiMaio F, Wang RY-R, Kim D, Miles C, Brunette TJ, Thompson J, Baker D (2013) High-resolution comparative modeling with RosettaCM. Structure 21:1735–1742

    CAS  PubMed  Google Scholar 

  • Sridhar A, Ross GA, Biggin PC (2017) Waterdock 2.0: water placement prediction for holo-structures with a PYMOL plugin. PLoS ONE 12:e0172743

    PubMed  PubMed Central  Google Scholar 

  • Standfuss J, Edwards PC, D’Antona A, Fransen M, Xie G, Oprian DD, Schertler GFX (2011) The structural basis of agonist-induced activation in constitutively active rhodopsin. Nature 471:656–660

    CAS  PubMed  PubMed Central  Google Scholar 

  • Strambi A, Coto PB, Frutos LM, Ferré N, Olivucci M (2008) Relationship between the excited state relaxation paths of rhodopsin and isorhodopsin. J Am Chem Soc 130:3382–3388

    CAS  PubMed  Google Scholar 

  • Struts AV, Salgado GF, Brown MF (2011) Solid-state 2H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin. Proc Natl Acad Sci USA 108:8263–8268

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sumita M, Ryazantsev MN, Saito K (2009) Acceleration of the Z to E photoisomerization of penta-2,4-dieniminium by hydrogen out-of-plane motion: theoretical study on a model system of retinal protonated Schiff base. Phys Chem Chem Phys 11:6406–6414

    CAS  PubMed  Google Scholar 

  • Suomivuori C-M, Gamiz-Hernandez AP, Sundholm D, Kaila VR (2017) Energetics and dynamics of a light-driven sodium-pumping rhodopsin. Proc Natl Acad Sci USA 114:7043–7048

    CAS  PubMed  PubMed Central  Google Scholar 

  • Svensson M, Humbel S, Froese RDJ, Matsubara T, Sieber S, Morokuma K (1996) ONIOM: a multilayered integrated MO + MM method for geometry optimizations and single point energy predictions. A test for Diels–Alder reactions and Pt(P(t-Bu)3)2 + H2 oxidative addition. J Phys Chem 100:19357–19363

    CAS  Google Scholar 

  • Tajkhorshid E, Suhai S (2000) The dielectric effect of the environment on the pK a of the retinal Schiff base and on the stabilization of the ion pair in bacteriorhodopsin. J Mol Struct: THEOCHEM 501:297–313

    Google Scholar 

  • Tajkhorshid E, Paizs B, Suhai S (1997) Conformational effects on the proton affinity of the Schiff base in bacteriorhodopsin: a density functional study. J Phys Chem B 101:8021–8028

    CAS  Google Scholar 

  • Tajkhorshid E, Baudry J, Schulten K, Suhai S (2000) Molecular dynamics study of the nature and origin of retinal’s twisted structure in bacteriorhodopsin. Biophys J 78:683–693

    CAS  PubMed  PubMed Central  Google Scholar 

  • Takemoto M, Kato HE, Koyama M, Ito J, Kamiya M, Hayashi S, Maturana AD, Deisseroth K, Ishitani R, Nureki O (2015) Molecular dynamics of channelrhodopsin at the early stages of channel opening. PLoS ONE 10:e0131094

    PubMed  PubMed Central  Google Scholar 

  • Tavanti F, Tozzini V (2014) A multi-scale–multi-stable model for the rhodopsin photocycle. Molecules 19:14961–14978

    PubMed  PubMed Central  Google Scholar 

  • Thomas YG, Szundi I, Lewis JW, Kliger DS (2009) Microsecond time-resolved circular dichroism of rhodopsin photointermediates. Biochemistry 48:12283–12289

    CAS  PubMed  Google Scholar 

  • Tikhonova IG, Selvam B, Ivetac A, Wereszczynski J, McCammon JA (2013) Simulations of biased agonists in the β 2 adrenergic receptor with accelerated molecular dynamics. Biochemistry 52:5593–5603

    CAS  PubMed  Google Scholar 

  • Tomasello G, Olaso-González G, Altoè P, Stenta M, Serrano-Andrés L, Merchán M, Orlandi G, Bottoni A, Garavelli M (2009) Electrostatic control of the photoisomerization efficiency and optical properties in visual pigments: on the role of counterion quenching. J Am Chem Soc 131:5172–5186

    CAS  PubMed  Google Scholar 

  • Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ulmschneider JP, Ulmschneider MB (2009) Sampling efficiency in explicit and implicit membrane environments studied by peptide folding simulations. Proteins 75:586–597

    CAS  PubMed  Google Scholar 

  • Van Keulen SC, Solano A, Rothlisberger U (2017) How rhodopsin tunes the equilibrium between protonated and deprotonated forms of the retinal chromophore. J Chem Theory Comput 13:4524–4534

    PubMed  Google Scholar 

  • Vanni S, Neri M, Tavernelli I, Rothlisberger U (2010) A conserved protonation-induced switch can trigger “ionic-lock” formation in adrenergic receptors. J Mol Biol 397:1339–1349

    CAS  PubMed  Google Scholar 

  • Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J, Darian E, Guvench O, Lopes P, Vorobyov I, Mackerell AD Jr (2010) CHARMM general force field: a force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem 31:671–690

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vickery ON, Carvalheda CA, Zaidi SA, Pisliakov AV, Katritch V, Zachariae U (2018) Intracellular transfer of Na+ in an active-state G-protein-coupled receptor. Structure 26:171–180

    CAS  PubMed  Google Scholar 

  • Volkov O, Kovalev K, Polovinkin V, Borshchevskiy V, Bamann C, Astashkin R, Marin E, Popov A, Balandin T, Willbold D, Büldt G, Bamberg E, Gordelly V (2017) Structural insights into ion conduction by channelrhodopsin 2. Science 358:eaan8862

    PubMed  Google Scholar 

  • Vreven T, Morokuma K (2006) Hybrid methods: ONIOM (QM:MM) and QM/MM. Ann Rep Comput Chem 2:35–51

    CAS  Google Scholar 

  • Vyěmtal J, Vondrášek J (2010) Metadynamics as a tool for mapping the conformational and free-energy space of peptides—the alanine dipeptide case study. J Phys Chem B 114:5632–5642

    Google Scholar 

  • Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan A, Levit A, Lansu K, Schools ZL, Che T, Nichols DE, Shoiket BK, Dror RO, Roth BL (2017) Crystal structure of an LSD-bound human serotonin receptor. Cell 168:379–389

    Google Scholar 

  • Wang Q, Schoenlein RW, Peteanu LA, Mathies RA, Shank CV (1994) Vibrationally coherent photochemistry in the femtosecond primary event of vision. Science 266:422–424

    CAS  PubMed  Google Scholar 

  • Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general Amber force field. J Comput Chem 25:1157–1174

    CAS  PubMed  Google Scholar 

  • Wang L-P, Chen J, Van Voorhis T (2012) Systematic parametrization of polarizable force fields from quantum chemistry data. J Chem Theory Comput 9:452–460

    PubMed  Google Scholar 

  • Wanko M, Hoffmann M, Frähmcke J, Frauenheim T, Elstner M (2008a) Effect of polarization on the opsin shift in rhodopsins. 2. Empirical polarization models for proteins. J Phys Chem B 112:11468–11478

    CAS  PubMed  Google Scholar 

  • Wanko M, Hoffmann M, Frauenheim T, Elstner M (2008b) Effect of polarization on the opsin shift in rhodopsins. 1. A combined QM/QM/MM model for bacteriorhodopsin and pharaonis sensory rhodopsin II. J Phys Chem B 112:11462–11467

    CAS  PubMed  Google Scholar 

  • Warshel A, Chu Z (2001) Nature of the surface crossing process in bacteriorhodopsin: computer simulations of the quantum dynamics of the primary photochemical event. J Phys Chem B 105:9857–9871

    CAS  Google Scholar 

  • Weis WI, Kobilka BK (2018) The molecular basis of G protein–coupled receptor activation. Annu Rev Biochem 87:897–919

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wu S, Zhang Y (2008) MUSTER: improving protein sequence profile–profile alignments by using multiple sources of structure information. Proteins 72:547–556

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wu S, Skolnick J, Zhang Y (2007) Ab initio modeling of small proteins by iterative TASSER simulations. BMC Biol 5:17

    PubMed  PubMed Central  Google Scholar 

  • Xu D, Zhang Y (2011) Improving the physical realism and structural accuracy of protein models by a two-step atomic-level energy minimization. Biophys J 101:2525–2534

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yamada T, Yamato T, Mitaku S (2016) Forced unfolding mechanism of bacteriorhodopsin as revealed by coarse-grained molecular dynamics. Biophys J 111:2086–2098

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang J, Zhang Y (2015) I-TASSER server: new development for protein structure and function predictions. Nucl Acids Res 43:W174–W181

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y (2015) The I-TASSER suite: protein structure and function prediction. Nat Methods 12:7–8

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ye L, Neale C, Sljoka A, Lyda B, Pichugin D, Tsuchimura N, Larda ST, Pomès R, García AE, Ernst OP, Sunahara RK, Prosser RS (2018) Mechanistic insights into allosteric regulation of the A2A adenosine G protein-coupled receptor by physiological cations. Nat Commun 9:1372

    PubMed  PubMed Central  Google Scholar 

  • Yuan S, Filipek S, Palczewski K, Vogel H (2014) Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathway. Nat Commun 5:4733

    CAS  PubMed  Google Scholar 

  • Zhang L, Hermans J (1996) Hydrophilicity of cavities in proteins. Proteins 24:433–438

    CAS  PubMed  Google Scholar 

  • Zhang Y, Skolnick J (2004) SPICKER: a clustering approach to identify near-native protein folds. J Comput Chem 25:865–871

    CAS  PubMed  Google Scholar 

  • Zhou F, Windemuth A, Schulten K (1993) Molecular dynamics study of the proton pump cycle of bacteriorhodopsin. Biochemistry 32:2291–2306

    CAS  PubMed  Google Scholar 

  • Zhou X, Sundholm D, Wesołowski TA, Kaila VR (2014) Spectral tuning of rhodopsin and visual cone pigments. J Am Chem Soc 136:2723–2726

    CAS  PubMed  Google Scholar 

  • Zhu S, Brown MF, Feller SE (2013) Retinal conformation governs pK a of protonated Schiff base in rhodopsin activation. J Am Chem Soc 135:9391–9398

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zwanzig RW (1954) High-temperature equation of state by a perturbation method. I. Nonpolar gases. J Chem Phys 22:1420–1426

    CAS  Google Scholar 

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Funding

This work was supported by the US National Institutes of Health (EY012049 and EY02604) and by the US National Science Foundation (MCB 1817862 and CHE 1904125) (to M.F.B.). A.V.S. was supported by the Russian Foundation for Basic Research (Grant 16-04-00494A). M.N.R. was supported by the Skolkovo Foundation (Grant agreement for Russian educational and scientific organization No. 7 dd 19.12.2017) and the Skolkovo Institute of Science and Technology (General agreement No. 3663-MRA dd 25.12.2017).

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Authors and Affiliations

  1. Institute of Chemistry, Saint Petersburg State University, 26 Universitetskii pr, Saint Petersburg, Russia, 198504

    Mikhail N. Ryazantsev

  2. Saint-Petersburg Academic University – Nanotechnology Research and Education Centre RAS, Saint Petersburg, Russia, 194021

    Dmitrii M. Nikolaev

  3. Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA

    Andrey V. Struts & Michael F. Brown

  4. Laboratory of Biomolecular NMR, Saint Petersburg State University, Saint Petersburg, Russia, 199034

    Andrey V. Struts

  5. Department of Physics, University of Arizona, Tucson, AZ, 85721, USA

    Michael F. Brown

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  1. Mikhail N. Ryazantsev
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  2. Dmitrii M. Nikolaev
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  3. Andrey V. Struts
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Correspondence to Michael F. Brown.

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Ryazantsev, M.N., Nikolaev, D.M., Struts, A.V. et al. Quantum Mechanical and Molecular Mechanics Modeling of Membrane-Embedded Rhodopsins. J Membrane Biol 252, 425–449 (2019). https://doi.org/10.1007/s00232-019-00095-0

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