Reproducing the Ensemble Average Polar Solvation Energy of a Protein from a Single Structure: Gaussian-Based Smooth Dielectric Function for Macromolecular Modeling.
Reproducing the Ensemble Average Polar Solvation Energy of a Protein from a Single Structure: Gaussian-Based Smooth Dielectric Function for Macromolecular Modeling.
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DOI：
10.1021/acs.jctc.7b00756
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发表时间：
2018-02-13
影响因子：
5.5
通讯作者：
Alexov, Emil
中科院分区：
文献类型：
--
作者：
Chakravorty, Arghya;Jia, Zhe;Li, Lin;Zhao, Shan;Alexov, Emil
通常，使用分子动力学（MD）或蒙特卡罗（MC）模拟来计算大分子的整体平均极性组分的溶剂化能，然后在每个快照上进行单一/刚性构象的溶剂化能计算。这项工作的主要目标是证明基于泊松-玻尔兹曼（PB）的方法使用基于高斯的光滑介电函数进行大分子建模，之前由我们（Li等人）开发。化学计算学报，2013,9(4),2126-2136)可以从一个单一的结构中复制一个蛋白质的集合平均值。我们表明，基于高斯的介电模型再现了蛋白质的能量最小化结构的系综平均值，而不管最小化环境（真空中最小化的结构，隐式或显式水或晶体结构），然而，最好的情况是当它与真空中最小化的结构配对时。在其他最小化环境（隐式或显式水或晶体结构）中，仍然可以选择传统的双介质模型，该模型产生正确的溶剂化能。我们在这项工作中的观察反映了适当模拟残基运动的能力，特别是盐桥残基的运动，如何影响电介质模型从单个真空最小化结构中重现极性溶剂化自由能的总体平均值的能力。
Typically, the ensemble average polar component of solvation energy of a macromolecule is computed using molecular dynamics (MD) or Monte Carlo (MC) simulations to generate conformational ensemble and then single/rigid conformation solvation energy calculation is performed on each of snapshots. The primary objective of this work is to demonstrate that Poisson-Boltzmann (PB) based approach using a Gaussian-based smooth dielectric function for macromolecular modeling previously developed by us (Li et al. J Chem Theory Comput 2013, 9 (4), 2126-2136) can reproduce the ensemble average of a protein from a single structure. We show that the Gaussian-based dielectric model reproduces the ensemble average from an energy minimized structure of a protein regardless of the minimization environment (structure minimized in vacuo, implicit or explicit waters or crystal structure), the best case, however, is when it is paired with an in vacuo minimized structure. In other minimization environments (implicit or explicit waters or crystal structure) the traditional two-dielectric model can still be selected with which the model produces correct solvation energies. Our observations from this work reflect how the ability to appropriately mimic the motion of residues, especially the salt-bridges residues, influences a dielectric model’s ability to reproduce the ensemble average value of polar solvation free energy from a single in vacuo minimized structure.
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影响因子：
3
作者：
Chakavorty, Arghya;Li, Lin;Alexov, Emil
通讯作者：
Alexov, Emil
影响因子：
5.5
作者：
Li, Lin;Li, Chuan;Zhang, Zhe;Alexov, Emil
通讯作者：
Alexov, Emil
影响因子：
5.5
作者：
Felts, Anthony K.;Gallicchio, Emilio;Levy, Ronald M.
通讯作者：
Levy, Ronald M.
影响因子：
3
作者：
Mongan, J;Case, DA;McCammon, JA
通讯作者：
McCammon, JA
影响因子：
3.3
作者：
Mobley, David L.;Dill, Ken A.;Chodera, John D.
通讯作者：
Chodera, John D.