Secondary structure bias in generalized born solvent models: Comparison of conformational ensembles and free energy of solvent polarization from explicit and implicit solvation
Secondary structure bias in generalized born solvent models: Comparison of conformational ensembles and free energy of solvent polarization from explicit and implicit solvation
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DOI：
10.1021/jp066831u
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发表时间：
2007-02-22
影响因子：
3.3
通讯作者：
Simmerling, Carlos
中科院分区：
文献类型：
--
作者：
Roe, Daniel R.;Okur, Asim;Simmerling, Carlos
通过用显式TIP3P溶剂对数百纳秒收敛的副本交换分子动力学(REMD)模拟与用GB溶剂模型进行的REMD模拟比较，研究了三种广义Born(GB)隐式溶剂模型对简单聚丙氨酸多肽热力学的影响。结果发现，与使用TIP3P的REMD模拟相比，GB的REMD模拟在二级结构布居方面存在显著差异，最显著的是α-螺旋二级结构的过量。通过比较TIP3P(热力学积分计算)、GB模型和基于泊松方程(PE)的隐式溶剂模型在溶剂化自由能的静电分量(Delta Delta G(Pol))上的差异，对这种差异进行了探讨。用每种溶剂模型计算了AlLa10的四种典型构象的溶剂化自由能的静电分量。由于发现PE模型在再现TIP3P Delta Delta G(POL)值方面具有最好的性能，因此将GB模型的有效出生半径与用PE计算的有效出生半径(所谓的完美半径)进行比较，并且在所有GB模型中都发现GB半径与完美半径之间存在显著且大量的偏差。讨论了这些偏差对溶剂化自由能的影响，结果表明，即使使用理想半径，GB与TIP3P Delta Delta G(POL)值的一致性也不会提高。这表明对有效出生半径计算的优化是有限的，未来提高GB模型精度的努力必须超越这种优化。
The effects of the use of three generalized Born (GB) implicit solvent models on the thermodynamics of a simple polyalanine peptide are studied via comparing several hundred nanoseconds of well-converged replica exchange molecular dynamics (REMD) simulations using explicit TIP3P solvent to REMD simulations with the GB solvent models. It is found that when compared to REMD simulations using TIP3P the GB REMD simulations contain significant differences in secondary structure populations, most notably an overabundance of alpha-helical secondary structure. This discrepancy is explored via comparison of the differences in the electrostatic component of the free energy of solvation (Delta Delta G(pol)) between TIP3P (via thermodynamic Integration calculations), the GB models, and an implicit solvent model based on the Poisson equation (PE). The electrostatic components of the solvation free energies are calculated using each solvent model for four representative conformations of Ala10. Since the PE model is found to have the best performance with respect to reproducing TIP3P Delta Delta G(pol) values, effective Born radii from the GB models are compared to effective Born radii calculated with PE (so-called perfect radii), and significant and numerous deviations in GB radii from perfect radii are found in all GB models. The effect of these deviations on the solvation free energy is discussed, and it is shown that even when perfect radii are used the agreement of GB with TIP3P Delta Delta G(pol) values does not improve. This suggests a limit to the optimization of the effective Born radius calculation and that future efforts to improve the accuracy of GB models must extend beyond such optimizations.