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Characterizing the function of domain linkers in regulating the dynamics of multi‐domain fusion proteins by microsecond molecular dynamics simulations and artificial intelligence Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-23 Bo Wang; Zhaoqian Su; Yinghao Wu
Multi‐domain proteins are not only formed through natural evolution but can also be generated by recombinant DNA technology. Because many fusion proteins can enhance the selectivity of cell targeting, these artificially produced molecules, called multi‐specific biologics, are promising drug candidates, especially for immunotherapy. Moreover, the rational design of domain linkers in fusion proteins
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A large‐scale survey of pairwise epistasis reveals a mechanism for evolutionary expansion and specialization of PDZ domains Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-23 David Nedrud; Willow Coyote‐Maestas; Daniel Schmidt
Deep mutational scanning (DMS) facilitates data‐driven models of protein structure and function. Here, we adapted Saturated Programmable Insertion Engineering (SPINE) as a programmable DMS technique. We validate SPINE with a reference single mutant dataset in the PSD95 PDZ3 domain and then characterize most pairwise double mutants to study epistasis. We observe wide‐spread proximal negative epistasis
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Investigating the folding mechanism of the N‐terminal domain of ribosomal protein L9 Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-11 Haozhe Zhang; Haomiao Zhang; Changjun Chen
Protein folding is a popular topic in the life science. However, due to the limited sampling ability of experiments and simulations, the general folding mechanism is not yet clear to us. In this work, we study the folding of the N‐terminal domain of ribosomal protein L9 (NTL9) in detail by a mixing replica exchange molecular dynamics method. The simulation results are close to previous experimental
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A detailed mapping of the readily accessible disulphide bonds in the cortex of wool fibres Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-06 Jeffrey E. Plowman; Rachel E. Miller; Ancy Thomas; Anita J. Grosvenor; Duane P. Harland; Santanu Deb‐Choudhury
Trichocyte keratin intermediate filament proteins (keratins) and keratin associated proteins (KAPs) differ from their epithelial equivalents by having significantly more cysteine residues. Interactions between these cysteine residues within a mammalian fiber, and the putative regular organization of interactions are likely important for defining fiber mechanical properties, and thus biological functionality
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Structural analysis of the β‐sheet edge of peptide self‐assembly using a model protein Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-12 Shota Shiga; Koki Makabe
Peptides and proteins self‐assemble into β‐sheet‐rich fibrils, amyloid, which extends its structure by incorporating peptide/protein molecules from solution. At the elongation edge, the peptide/protein molecule binds to the edge of the amyloid β‐sheet. Such processes are transient and elusive when observing molecular details by experimental methods. We used a model protein system, peptide self‐assembly
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DeepCys: Structure‐based multiple cysteine function prediction method trained on deep neural network: Case study on domains of unknown functions belonging to COX2 domains Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-12 Vamsi Nallapareddy; Shubham Bogam; Himaja Devarakonda; Shubham Paliwal; Debashree Bandyopadhyay
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Crystallographic and modeling study of the human inorganic pyrophosphatase 1: A potential anti‐cancer drug target Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-13 Haiying Niu; Jiang Zhu; Quanxin Qu; Xia Zhou; Xiaolan Huang; Zhihua Du
Inorganic pyrophosphatases (PPases) catalyze the hydrolysis of pyrophosphate to phosphates. PPases play essential roles in growth and development, and are found in all kingdoms of life. Human possess two PPases, PPA1 and PPA2. PPA1 is present in all tissues, acting largely as a housekeeping enzyme. Besides pyrophosphate hydrolysis, PPA1 can also directly dephosphorylate phosphorylated c‐Jun N‐terminal
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β‐sheet breakers with consecutive phenylalanines: Insights into mechanism of dissolution of β‐amyloid fibrils Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-06 Adam Jarmuła; Jan Ludwiczak; Dariusz Stępkowski
β‐sheet breakers (BSB) constitute a class of peptide inhibitors of amyloidogenesis, a process which is a hallmark of many diseases called amyloidoses, including Alzheimer's disease (AD); however, the molecular details of their action are still not fully understood. Here we describe the results of the computational investigation of the three BSBs, iaβ6 (LPFFFD), iaβ5 (LPFFD), and iaβ6_Gly (LPFGFD),
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Deep learning pan‐specific model for interpretable MHC‐I peptide binding prediction with improved attention mechanism Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-16 Jing Jin; Zhonghao Liu; Alireza Nasiri; Yuxin Cui; Stephen Louis; Ansi Zhang; Yong Zhao; Jianjun Hu
Accurate prediction of peptide binding affinity to the major histocompatibility complex (MHC) proteins has the potential to design better therapeutic vaccines. Previous work has shown that pan‐specific prediction algorithms can achieve better prediction performance than other approaches. However, most of the top algorithms are neural networks based black box models. Here, we propose DeepAttentionPan
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Combination of deep neural network with attention mechanism enhances the explainability of protein contact prediction Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-03 Chen Chen; Tianqi Wu; Zhiye Guo; Jianlin Cheng
Deep learning has emerged as a revolutionary technology for protein residue‐residue contact prediction since the 2012 CASP10 competition. Considerable advancements in the predictive power of the deep learning‐based contact predictions have been achieved since then. However, little effort has been put into interpreting the black‐box deep learning methods. Algorithms that can interpret the relationship
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Protein dynamics analysis identifies candidate cancer driver genes and mutations in TCGA data Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-07 Jan Fehmi Sayılgan; Türkan Haliloğlu; Mehmet Gönen
Recently, it has been showed that cancer missense mutations selectively target the neighborhood of hinge residues, which are key sites in protein dynamics. Here, we show that this approach can be extended to find previously unknown candidate mutations and genes. To this aim, we developed a computational pipeline to detect significantly enriched three‐dimensional (3D) clustering of missense mutations
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Thermodynamic stability of hnRNP A1 low complexity domain revealed by high‐pressure NMR Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-06 Jeffrey D. Levengood; Jake Peterson; Blanton S. Tolbert; Julien Roche
We have investigated the pressure‐ and temperature‐induced conformational changes associated with the low complexity domain of hnRNP A1, an RNA‐binding protein able to phase separate in response to cellular stress. Solution NMR spectra of the hnRNP A1 low‐complexity domain fused with protein‐G B1 domain were collected from 1 to 2500 bar and from 268 to 290 K. While the GB1 domain shows the typical
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Potential of Mean Force and Umbrella Sampling Simulation for the Transport of 5‐Oxazolidinone in Heterotetrameric Sarcosine Oxidase Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-11 Shigetaka Yoneda; Takami Saito; Daisuke Nakajima; Go Watanabe
The structure of heterotetrameric sarcosine oxidase (HSO) contains a highly complex system composed of a large cavity and tunnels, which are essential for the reaction and migration of the reactants, products, and intermediates. Previous geometrical analysis using the CAVER program has predicted that there are three possible tunnels, T1, T2, and T3, for the exit pathway of the iminium intermediate
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Investigation of the aquaporin‐2 gating mechanism with molecular dynamics simulations Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-11 Hooman Hadidi; Reza Kamali; Alireza Binesh
Aquaporin‐2 plays a vital role in the human kidney as a water passage channel. Any disorder with its function can cause water imbalance and consequently disease in humans, especially nephrogenic diabetes insipidus (NDI). For this reason, an accurate understanding of its performance can be useful for therapeutic purposes. In this paper, we investigate the gating mechanism induced by spontaneous fluctuations
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Oxidation shuts down an auto‐inhibitory mechanism of von Willebrand factor Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-06 Rachel Tsai; Gianluca Interlandi
The blood protein von Willebrand factor (VWF) is a key link between inflammation and pathological thrombus formation. In particular, oxidation of methionine residues in specific domains of VWF due to the release of oxidants in inflammatory conditions has been linked to an increased platelet‐binding activity. However, the atomistic details of how methionine oxidation activates VWF have not been elucidated
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A survey of human histone H1 subtypes interaction networks: implications for histones H1 functioning Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-02-06 Andrzej Kowalski
To show a spectrum of histone H1 subtypes (H1.1 ‐ H1.5) activity realized through the protein‐protein interactions, data selected from APID resources were processed with sequence‐based bioinformatics approaches. Histone H1 subtypes participate in over half a thousand interactions with nuclear and cytosolic proteins (ComPPI database) engaged in the enzymatic activity and binding of nucleic acids and
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In silico screening and molecular dynamics simulation of deleterious PAH mutations responsible for phenylketonuria genetic disorder Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-25 Andrea Lopez; Brandon Havranek; George A. Papadantonakis; Shahidul M. Islam
Phenylketonuria (PKU) is a genetic disorder that if left untreated can lead to behavioral problems, epilepsy, and even mental retardation. PKU results from mutations within the phenylalanine‐4‐hydroxylase (PAH) gene that encodes for the PAH protein. The study of all PAH causing mutations is improbable using experimental techniques. In this study, a collection of in silico resources, sorting intolerant
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Robust principal component analysis‐based prediction of protein‐protein interaction hot spots Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-17 Divya Sitani; Alejandro Giorgetti; Mercedes Alfonso‐Prieto; Paolo Carloni
Proteins often exert their function by binding to other cellular partners. The hot spots are key residues for protein‐protein binding. Their identification may shed light on the impact of disease associated mutations on protein complexes and help design protein‐protein interaction inhibitors for therapy. Unfortunately, current machine learning methods to predict hot spots, suffer from limitations caused
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New amino acid substitution matrix brings sequence alignments into agreement with structure matches Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-20 Kejue Jia; Robert L Jernigan
Protein sequence matching presently fails to identify many structures that are highly similar, even when they are known to have the same function. The high packing densities in globular proteins lead to interdependent substitutions, which have not previously been considered for amino acid similarities. At present, sequence matching compares sequences based only upon the similarities of single amino
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Protein structure search to support the development of protein structure prediction methods Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-18 Ronald Ayoub; Yugyung Lee
Protein structure prediction is a long‐standing unsolved problem in molecular biology that has seen renewed interest with the recent success of deep learning with AlphaFold at CASP13. While developing and evaluating protein structure prediction methods, researchers may want to identify the most similar known structures to their predicted structures. These predicted structures often have low sequence
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Study on functional sites in human multidrug resistance protein 1 (hMRP1) Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-19 Junmei He; Zhongjie Han; Qurat ul Ain Farooq; Chunhua Li
Human multidrug resistance protein 1 (hMRP1) is an important member of the ATP‐binding cassette (ABC) transporter superfamily. It can extrude a variety of anticancer drugs and physiological organic anions across the plasma membrane, which is activated by substrate binding, and is accompanied by large‐scale cooperative movements between different domains. Currently, it remains unclear completely about
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Estimating the accuracy of pharmacophore‐based detection of cognate receptor‐ligand pairs in the immunoglobulin superfamily Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-23 Nelson Gil; Rojan Shrestha; Andras Fiser
Secreted and membrane‐bound members of the immunoglobulin superfamily (IgSF) encompass a large, diverse array of proteins that play central roles in immune response and neural development, and are implicated in diseases ranging from cancer to rheumatoid arthritis. Despite the potential biomedical benefits of understanding IgSF:IgSF cognate receptor‐ligand interactions, relatively little about them
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Exploration of key residues and conformational change of anti‐terminator protein GlpP for ligand and RNA binding Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-17 Qiaoqing Chen; Wenjing Cui; Zhemin Zhou; Laichuang Han
Anti‐terminator protein GlpP regulates gene expression of glycerol uptake operon at post‐transcriptional level in a number of bacteria. By now, the molecular dynamics details of ligand and RNA binding by GlpP are still obscure. In this study, we employed the molecular dynamic (MD) simulation and constructed a functional verification platform of GlpP to resolve these puzzles. By combining molecular
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Mycobacterium tuberculosis puromycin hydrolase displays a prolyl oligopeptidase fold and an acyl aminopeptidase activity Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-10 YuanHao Zhao; Qiaoli Feng; Xiao Zhou; Yan Zhang; Maxwell Lukman; Jie Jiang; David Ruiz‐Carrillo
Puromycin‐hydrolizing peptidases have been described as members of the prolyl oligopeptidase peptidase family. These enzymes are present across all domains of life but still little is known of the homologs found in the pathogenic bacterium Mycobacterium tuberculosis. The crystal structure of a M. tuberculosis puromycin hydrolase peptidase has been determined at 3 Angstrom resolution, revealing a conserved
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Positional preferences in flavonoids for inhibition of ribonuclease A: Where “?OH” where? Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-09 Debi Ranjan Tripathy; Atashi Panda; Amit Kumar Dinda; Swagata Dasgupta
Flavonoids are a class of polyphenols that possess diverse properties. The structure‐activity relationship of certain flavonoids and resveratrol with ribonuclease A (RNase A) has been investigated. The selected flavonoids have a similar skeleton and the positional preferences of the phenolic moieties toward inhibition of the catalytic activity of RNase A have been studied. The results obtained for
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Human SARS CoV‐2 spike protein mutations Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-09 Lalitha Guruprasad
The human spike protein sequences from Asia, Africa, Europe, North America, South America, and Oceania were analyzed by comparing with the reference severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) protein sequence from Wuhan‐Hu‐1, China. Out of 10333 spike protein sequences analyzed, 8155 proteins comprised one or more mutations. A total of 9654 mutations were observed that correspond
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Insights into specificity and catalytic mechanism of amphotericin B/nystatin thioesterase Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2021-01-02 Rufan Wang; Wentao Tao; Lei Liu; Chen Li; Linquan Bai; Yi‐Lei Zhao; Ting Shi
Polyene polyketides amphotericin B (AMB) and nystatin (NYS) are important antifungal drugs. Thioesterases (TEs), located at the last module of PKS, control the release of polyketides by cyclization or hydrolysis. Intrigued by the tiny structural difference between AMB and NYS, as well as the high sequence identity between AMB TE and NYS TE, we constructed four systems to study the structural characteristics
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Mind the GAP: Purification and characterization of urea resistant GAPDH during extreme dehydration Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-12-24 Hanane Hadj‐Moussa; Steven C. Wade; Christine L. Childers; Kenneth B. Storey
The African clawed frog (Xenopus laevis) withstands prolonged periods of extreme whole‐body dehydration that lead to impaired blood flow, global hypoxia, and ischemic stress. During dehydration, these frogs shift from oxidative metabolism to a reliance on anaerobic glycolysis. In this study, we purified the central glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) to electrophoretic
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Ca2+ as cofactor of the mitochondrial H+‐translocating F1FO‐ATP(hydrol)ase Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-12-30 Salvatore Nesci; Alessandra Pagliarani
The mitochondrial F1FO‐ATPase in the presence of the natural cofactor Mg2+ acts as the enzyme of life by synthesizing ATP, but it can also hydrolyze ATP to pump H+. Interestingly, Mg2+ can be replaced by Ca2+, but only to sustain ATP hydrolysis and not ATP synthesis. When Ca2+ inserts in F1, the torque generation built by the chemomechanical coupling between F1 and the rotating central stalk was reported
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Using normal mode analysis on protein structural models. How far can we go on our predictions? Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-12-21 Nuria Cirauqui Diaz; Elisa Frezza; Juliette Martin
Normal mode analysis (NMA) is a fast and inexpensive approach that is largely used to gain insight into functional protein motions, and more recently to create conformations for further computational studies. However, when the protein structure is unknown, the use of computational models is necessary. Here, we analyze the capacity of NMA in internal coordinate space to predict protein motion, its intrinsic
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Hierarchical, rotation‐equivariant neural networks to select structural models of protein complexes Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-12-02 Stephan Eismann; Raphael J.L. Townshend; Nathaniel Thomas; Milind Jagota; Bowen Jing; Ron O. Dror
Predicting the structure of multi‐protein complexes is a grand challenge in biochemistry, with major implications for basic science and drug discovery. Computational structure prediction methods generally leverage predefined structural features to distinguish accurate structural models from less accurate ones. This raises the question of whether it is possible to learn characteristics of accurate models
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Ligand‐induced transition in conformations of vicinal cysteine disulfides in proteins Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-12-30 K Kasi Amarnath Reddy; Muddagoni Jayashree; Panchada Ch V Govindu; Konkallu Hanumae Gowd
Vicinal cysteine disulfides are thought to be associated with specific conformations of cysteine disulfides due to the restricted rotation of single bonds in an eight‐membered cyclic disulfide loop. Conformations of vicinal cysteine disulfides are analyzed using χ1, χ2, χ3, χ2′, χ1′ torsion angles in the crystal structures of proteins retrieved from protein data bank (PDB). 85% of vicinal disulfides
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Structural basis of mutants of PET‐degrading enzyme from Saccharomonospora viridis AHK190 with high activity and thermal stability Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-12-19 Miho Emori; Nobutaka Numoto; Akane Senga; Gert‐Jan Bekker; Narutoshi Kamiya; Yuma Kobayashi; Nobutoshi Ito; Fusako Kawai; Masayuki Oda
The cutinase‐like enzyme from the thermophile Saccharomonospora viridis AHK190, Cut190, is a good candidate to depolymerize polyethylene terephthalate (PET) efficiently. We previously developed a mutant of Cut190 (S226P/R228S), which we designated as Cut190* that has both increased activity and stability and solved its crystal structure. Recently, we showed that mutation of D250C/E296C on one of the
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Influence of sequence length and charged residues on Swc5 binding with histone H2A‐H2B Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-12-15 Wen‐Ting Chu; Jin Wang
SWR is a member of chromatin remodeler family and participates the replacement of histone H2A with H2A.Z. One of the SWR subunits, Swc5, has an intrinsically disordered region and binds to H2A‐H2B dimer. Though the binding structure of Swc5 and H2A‐H2B has been resolved recently, it is still challenging to investigate the binding mechanism as well as the role of the charge interactions between Swc5
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Lysine–arginine advanced glycation end‐product cross‐links and the effect on collagen structure: A molecular dynamics study Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-12-15 Anthony Nash; Sang Young Noh; Helen L. Birch; Nora H. de Leeuw
The accumulation of advanced glycation end‐products is a fundamental process that is central to age‐related decline in musculoskeletal tissues and locomotor system function and other collagen‐rich tissues. However, although computational studies of advanced glycation end‐product cross‐links could be immensely valuable, this area remains largely unexplored given the limited availability of structural
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Crystal structure of PYCH_01220 from Pyrococcus yayanosii potentially involved in binding nucleic acid Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-25 Haemin Noh; Jae‐Hyun Jeon; Yeon‐Gil Kim; Byung‐Ha Oh
We report the crystal structure of PYCH_01220, a hypothetical protein in Pyrococcus yayanosii CH1. This protein is composed of two domains, named Domain A and Domain B. While Domain B is not significantly homologous to known protein structures, Domain A is structurally analogous to the C‐terminal ribonuclease domain of Escherichia coli colicin D. Domain A has a positively charged surface patch rendered
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Effects of amino acid modifications on the permeability of the pentameric sarcolipin channel Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-27 Yipeng Cao; Rui Yang; Jiana Sun; Wenwen Zhang; Imshik Lee; Wei Wang; Xiangfei Meng
Sarcolipin (SLN) is an important transmembrane (TM) protein encoded by long noncoding RNA. SLN is expressed in the sarcoplasmic reticulum and regulates cardiac and skeletal muscle contractions. SLN forms a pentameric hydrophobic ligand‐gated ion channel. The protonation of Glu7 (protonated SLN, pSLN) and mutation of Thr18 to Ala18 (T18A) have been reported to exert a significant influence on the permeability
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Perturbing the energy landscape for improved packing during computational protein design Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-29 Jack B. Maguire; Hugh K. Haddox; Devin Strickland; Samer F. Halabiya; Brian Coventry; Jermel R. Griffin; Surya V. S. R. K Pulavarti; Matthew Cummins; David F Thieker; Eric Klavins; Thomas Szyperski; Frank DiMaio; David Baker; Brian Kuhlman
The FastDesign protocol in the molecular modeling program Rosetta iterates between sequence optimization and structure refinement to stabilize de novo designed protein structures and complexes. FastDesign has been used previously to design novel protein folds and assemblies with important applications in research and medicine. To promote sampling of alternative conformations and sequences, FastDesign
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Are granulins copper sequestering proteins? Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-30 Anukool A. Bhopatkar; Vijayaraghavan Rangachari
Granulins (GRN 1‐7) are short (~6 kDa), cysteine‐rich proteins that are generated upon the proteolytic processing of progranulin (PGRN). These peptides, along with their precursor, have been implicated in multiple pathophysiological roles, especially in neurodegenerative diseases. Previously we showed that GRN‐3 and GRN‐5 are fully disordered in the reduced form implicating redox sensitive attributes
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Purification, characterization, and crystal structure of YhdA‐type azoreductase from Bacillus velezensis Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-12-01 Amit Bafana; Farha Khan; Kaza Suguna
Azoreductases are being extensively investigated for their ability to initiate degradation of recalcitrant azo dyes through reduction of azo bonds. There is great interest in studying their diversity, structure, and function to facilitate better understanding and effective application. Current study reports azoreductase enzyme from Bacillus velezensis, which showed 69.5% identity to the Bacillus subtilis
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Persistent homology and application on residues 1 to 28 of amyloid beta peptide Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-26 Yaru Gao; Fengchun Lei; Shu Xiao Li
This article combines the principal component analysis (PCA) with persistent homology for applications in biomolecular data analysis. We extend the technique of persistent homology to localized weighted persistent homology to fit the properties of molecules. We introduce this novel PCA in the study of the folding process of residues 1 to 28 of amyloid beta peptide in solution. We are able to determine
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Predicting cryptic ligand binding sites based on normal modes guided conformational sampling Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-26 Wenjun Zheng
To greatly expand the druggable genome, fast and accurate predictions of cryptic sites for small molecules binding in target proteins are in high demand. In this study, we have developed a fast and simple conformational sampling scheme guided by normal modes solved from the coarse‐grained elastic models followed by atomistic backbone refinement and side‐chain repacking. Despite the observations of
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Prefusion spike protein stabilization through computational mutagenesis Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-24 Dong Yan Zhang; Jian Wang; Nikolay V. Dokholyan
A novel severe acute respiratory syndrome (SARS)‐like coronavirus (SARS‐CoV‐2) has emerged as a human pathogen, causing global pandemic and resulting in over 400 000 deaths worldwide. The surface spike protein of SARS‐CoV‐2 mediates the process of coronavirus entry into human cells by binding angiotensin‐converting enzyme 2 (ACE2). Due to the critical role in viral‐host interaction and the exposure
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Crystal structure of the large subunit of cobaltochelatase from Mycobacterium tuberculosis Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-18 Jia‐Hui Zhang; Hui Yuan; Xiao Wang; Huai‐En Dai; Min Zhang; Lin Liu
Cobaltochelatase in aerobic cobalamin biosynthesis is a complex composed of three subunits. The large subunit CobN is a 140‐kDa protein and is homologous to the ChlH subunit of magnesium chelatase. Previously we have reported the 2.5‐Å structure of a cyanobacterial ChlH. Here we present the 1.8‐Å structure of CobN from Mycobacterium tuberculosis. The overall structure of CobN and ChlH is similar, but
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Why are ACE2 binding coronavirus strains SARS‐CoV/SARS‐CoV‐2 wild and NL63 mild? Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-18 Puneet Rawat; Sherlyn Jemimah; P. K. Ponnuswamy; M. Michael Gromiha
Coronaviruses are responsible for several epidemics, including the 2002 SARS, 2012 MERS, and COVID‐19. The emergence of recent COVID‐19 pandemic due to SARS‐CoV‐2 virus in December 2019 has resulted in considerable research efforts to design antiviral drugs and other therapeutics against coronaviruses. In this context, it is crucial to understand the biophysical and structural features of the major
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Molecular dynamics simulations identify the regions of compromised thermostability in SazCA Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-04 Shashi Kumar; Deepak Seth; Parag Arvind Deshpande
The present study examined the structure and dynamics of the most active and thermostable carbonic anhydrase, SazCA, probed using molecular dynamics simulations. The molecular system was described by widely used biological force‐fields (AMBER, CHARMM22, CHARMM36, and OPLS‐AA) in conjunction with TIP3P water model. The comparison of molecular dynamics simulation results suggested AMBER to be a suitable
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Cover Image, Volume 88, Issue 12 Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-04
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Cover Image, Volume 88, Issue 12 Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-04
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Predicted structural differences of four fertility‐related Y‐chromosome proteins in Macaca mulatta, M. fascicularis, and their Indochinese hybrids Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-04 Cody A. Ruiz; Morgan E. Chaney; Masanori Imamura; Hiroo Imai; Anthony J. Tosi
Species in the genus Macaca typically live in multimale‐multifemale social groups with male macaques exhibiting some of the largest testis: body weight ratios among primates. Males are believed to experience intense levels of sperm competition. Several spermatogenesis genes are located on the Y‐chromosome and, interestingly, occasional hybridization between two species has led to the introgression
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Simplified geometric representations of protein structures identify complementary interaction interfaces Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-11-02 Caitlyn L. McCafferty; Edward M. Marcotte; David W. Taylor
Protein‐protein interactions are critical to protein function, but three‐dimensional (3D) arrangements of interacting proteins have proven hard to predict, even given the identities and 3D structures of the interacting partners. Specifically, identifying the relevant pairwise interaction surfaces remains difficult, often relying on shape complementarity with molecular docking while accounting for molecular
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Machine learning‐based prediction of enzyme substrate scope: Application to bacterial nitrilases Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-10-28 Zhongyu Mou; Jason Eakes; Connor J. Cooper; Carmen M. Foster; Robert F. Standaert; Mircea Podar; Mitchel J. Doktycz; Jerry M. Parks
Predicting the range of substrates accepted by an enzyme from its amino acid sequence is challenging. Although sequence‐ and structure‐based annotation approaches are often accurate for predicting broad categories of substrate specificity, they generally cannot predict which specific molecules will be accepted as substrates for a given enzyme, particularly within a class of closely related molecules
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PDB‐tools web: A user‐friendly interface for the manipulation of PDB files Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-10-27 Brian Jiménez‐García; João M. C. Teixeira; Mikael Trellet; João P. G. L. M. Rodrigues; Alexandre M. J. J. Bonvin
The Protein Data Bank (PDB) file format remains a popular format used and supported by many software to represent coordinates of macromolecular structures. It however suffers from drawbacks such as error‐prone manual editing. Because of that, various software toolkits have been developed to facilitate its editing and manipulation, but, to date, there is no online tool available for this purpose. Here
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Genomic screening and molecular dynamics simulations of cyanovirin‐N homologs from cyanobacteria phylum Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-10-17 Andrei Santos Siqueira; Alex Ranieri Jerônimo Lima; Delia Cristina Figueira Aguiar; Alberdan Silva Santos; Evonnildo Costa Gonçalves
The phylum cyanobacteria are one of the most ancient groups of organisms on the planet and are well recognized due to its wide distribution, ecological role, and biotechnological potential. Cyanobacterial lectins are being extensively explored due to their antiviral activity, mainly because of their capacity of inhibiting HIV strains from infecting human cells by gp120 and gp41 binding. Cianovirin‐N
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Tuning the binding interface between Machupo virus glycoprotein and human transferrin receptor Proteins Struct. Funct. Bioinform. (IF 2.828) Pub Date : 2020-10-17 Dick J Sjöström; Anneli Lundgren; Scott J Garforth; Sinisa Bjelic
Machupo virus, known to cause hemorrhagic fevers, enters human cells via binding with its envelope glycoprotein to transferrin receptor 1 (TfR). Similarly, the receptor interactions have been explored in biotechnological applications as a molecular system to ferry therapeutics across the cellular membranes and through the impenetrable blood–brain barrier that effectively blocks any such delivery into