Accurate Estimation of pKb Values for Amino Groups from Surface Electrostatic Potential (VS,min) Calculations. The Isoelectric Points of Amino Acids as a Case Study.,Journal of Chemical Information and Modeling

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Accurate Estimation of pKb Values for Amino Groups from Surface Electrostatic Potential (VS,min) Calculations. The Isoelectric Points of Amino Acids as a Case Study.
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2020-02-28 , DOI: 10.1021/acs.jcim.9b01173
Jacinto Sandoval-Lira _{1,

2} , Gustavo Mondragón-Solórzano _{1,

2} , Leonardo I Lugo-Fuentes ₃ , Joaquín Barroso-Flores _{1,

2}

Affiliation

Theoretical calculation of equilibrium dissociation constants is a very computationally demanding and time-consuming process since it requires an extremely accurate computation of the solvation Free Energy changes for each of the species involved.By correlating the minimum surface electrostatic potential (VS,min) on the Nitrogen atom of several aliphatic amino groups-calculated at the DFTωB97X-D/cc-pVDZ level of theory-we obtained regression models for each kind of substitution patternfrom which we interpolate their corresponding pKb values with a remarkable accuracy: primary R2= 0.9519; secondary R2 = 0.9112; and tertiary R2 = 0.8172 (N = 20 for each family). These models were validated with tests sets (N = 5) with MAE values of 0.1213 (primary), 0.4407 (secondary), and 0.3057 (tertiary). Combining this ansatz with another previously reported by our group to estimate pKa values1 we are able to reproduce the isoelectric point of 13 amino acids with no titrable sidechains with MAE = 0.4636 pI units.

中文翻译：

根据表面静电势（VS，min）计算准确估计氨基的pKb值。氨基酸的等电点作为案例研究。

平衡解离常数的理论计算是一个计算上非常耗时且费时的过程，因为它需要极其精确地计算出所涉及的每个物种的溶剂化自由能变化。通过关联表面上的最小表面静电势（VS，min）在理论的DFTωB97X-D/ cc-pVDZ水平上计算的几个脂肪族氨基的氮原子，我们获得了每种取代模式的回归模型，从中可以插值其相应的pKb值，且准确性极高：一级R2 = 0.9519；次级R2 = 0.9112; 三级R2 = 0.8172（每个家庭N = 20）。这些模型通过测试集（N = 5）进行了验证，MAE值分别为0.1213（主要），0.4407（次要）和0.3057（三次）。

更新日期：2020-02-28

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