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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- 作者：Daniel R. Roe ; Asim Okur ; Lauren Wickstrom ; Viktor Hornak ; Carlos Simmerling
- 刊名：Journal of Physical Chemistry B
- 出版年：2007
- 出版时间：February 22, 2007
- 年：2007
- 卷：111
- 期：7
- 页码：1846 - 1857
- 全文大小：235K
- 年卷期：v.111,no.7(February 22, 2007)
- ISSN：1520-5207
文摘
The effects of the use of three generalized Born (GB) implicit solvent models on the thermodynamics of asimple polyalanine peptide are studied via comparing several hundred nanoseconds of well-converged replicaexchange molecular dynamics (REMD) simulations using explicit TIP3P solvent to REMD simulations withthe GB solvent models. It is found that when compared to REMD simulations using TIP3P the GB REMDsimulations contain significant differences in secondary structure populations, most notably an overabundanceof 
-helical secondary structure. This discrepancy is explored via comparison of the differences in theelectrostatic component of the free energy of solvation (
Gpol) between TIP3P (via thermodynamic Integrationcalculations), the GB models, and an implicit solvent model based on the Poisson equation (PE). Theelectrostatic components of the solvation free energies are calculated using each solvent model for fourrepresentative conformations of Ala10. Since the PE model is found to have the best performance with respectto reproducing TIP3P Gpol values, effective Born radii from the GB models are compared to effectiveBorn radii calculated with PE (so-called perfect radii), and significant and numerous deviations in GB radiifrom perfect radii are found in all GB models. The effect of these deviations on the solvation free energy isdiscussed, and it is shown that even when perfect radii are used the agreement of GB with TIP3P Gpolvalues does not improve. This suggests a limit to the optimization of the effective Born radius calculationand that future efforts to improve the accuracy of GB models must extend beyond such optimizations.
-helical secondary structure. This discrepancy is explored via comparison of the differences in theelectrostatic component of the free energy of solvation (Gpol) between TIP3P (via thermodynamic Integrationcalculations), the GB models, and an implicit solvent model based on the Poisson equation (PE). Theelectrostatic components of the solvation free energies are calculated using each solvent model for fourrepresentative conformations of Ala10. Since the PE model is found to have the best performance with respectto reproducing TIP3P Gpol values, effective Born radii from the GB models are compared to effectiveBorn radii calculated with PE (so-called perfect radii), and significant and numerous deviations in GB radiifrom perfect radii are found in all GB models. The effect of these deviations on the solvation free energy isdiscussed, and it is shown that even when perfect radii are used the agreement of GB with TIP3P Gpolvalues does not improve. This suggests a limit to the optimization of the effective Born radius calculationand that future efforts to improve the accuracy of GB models must extend beyond such optimizations.