A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations
A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations
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DOI：
10.1002/jcc.10349
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发表时间：
2003-12-01
影响因子：
3
通讯作者：
Kollman, P
中科院分区：
文献类型：
--
作者：
Duan, Y;Wu, C;Kollman, P
分子力学模型已广泛应用于蛋白质和核酸动力学的研究。在这里，我们报告的第三代点电荷的蛋白质全原子力场的发展。遵循康奈尔等人的早期方法，通过拟合使用B3 LYP/cc-pVTZ//HF/6- 31 G ** 量子力学方法计算的二肽的静电势获得电荷组。通过拟合使用MP2/cc-PVTZ//HF/6- 31 G ** 量子力学方法计算的Ace-Ala-Nme和Ace-Gly-Nme二肽的能量分布来获得主链扭转参数。所有其他参数均取自现有的AMBER数据库。与先前力场的主要区别在于，所有量子力学计算都是在凝聚相中进行的，具有连续溶剂模型和有效介电常数ε = 4。我们预计，这个力场参数集将解决某些关键的短距离以前的力场在蛋白质的凝聚相模拟。对肽的初步测试表明，对于Ace-Gly-Nme和Ace-Ala-Nme二肽，计算的和统计学测量的Ramanchandran图之间具有高度的相似性。我们的结果的一些亮点包括（1）之间的扩展和螺旋区域分布的平衡，以及（2）有利的II型聚脯氨酸螺旋区与最近的实验一致。新的和康奈尔等人的电荷集之间的向后兼容性。如通过偶极矩之间的总体一致性所判断的，允许在配体结合计算区域中平滑过渡到新的力场。一个大的蛋白质组上的测试模拟也进行了讨论。(C)2003 Wiley Periodicals，Inc.
Molecular mechanics models have been applied extensively to study the dynamics of proteins and nucleic acids. Here we report the development of a third-generation point-charge all-atom force field for proteins. Following the earlier approach of Cornell et al., the charge set was obtained by fitting to the electrostatic potentials of dipeptides calculated using B3LYP/cc-pVTZ//HF/6-31G** quantum mechanical methods. The main-chain torsion parameters were obtained by fitting to the energy profiles of Ace-Ala-Nme and Ace-Gly-Nme di-peptides calculated using MP2/cc-PVTZ//HF/6-31G** quantum mechanical methods. All other parameters were taken from the existing AMBER data base. The major departure from previous force fields is that all quantum mechanical calculations were done in the condensed phase with continuum solvent models and an effective dielectric constant of epsilon = 4. We anticipate that this force field parameter set will address certain critical short comings of previous force fields in condensed-phase simulations of proteins. Initial tests on peptides demonstrated a high-degree of similarity between the calculated and the statistically measured Ramanchandran maps for both Ace-Gly-Nme and Ace-Ala-Nme di-peptides. Some highlights of Our results include (1) well-preserved balance between the extended and helical region distributions, and (2) favorable type-II poly-proline helical region in agreement with recent experiments. Backward compatibility between the new and Cornell et al. charge sets. as judged by overall agreement between dipole moments, allows a smooth transition to the new force field in the area of ligand-binding calculations. Test simulations on a large set of proteins are also discussed. (C) 2003 Wiley Periodicals, Inc.