Felts Anthony K, Gallicchio Emilio, Chekmarev Dmitriy, Paris Kristina A, Friesner Richard A, Levy Ronald M
Department of Chemistry and Chemical Biology and BioMaPS Institute for Quantitative Biology, Rutgers University, Piscataway, New Jersey 08854.
J Chem Theory Comput. 2008;4(5):855-868. doi: 10.1021/ct800051k.
The OPLS-AA all-atom force field and the Analytical Generalized Born plus Non-Polar (AGBNP) implicit solvent model, in conjunction with torsion angle conformational search protocols based on the Protein Local Optimization Program (PLOP), are shown to be effective in predicting the native conformations of 57 9-residue and 35 13-residue loops of a diverse series of proteins with low sequence identity. The novel nonpolar solvation free energy estimator implemented in AGBNP augmented by correction terms aimed at reducing the occurrence of ion pairing are important to achieve the best prediction accuracy. Extended versions of the previously developed PLOP-based conformational search schemes based on calculations in the crystal environment are reported that are suitable for application to loop homology modeling without the crystal environment. Our results suggest that in general the loop backbone conformation is not strongly influenced by crystal packing. The application of the temperature Replica Exchange Molecular Dynamics (T-REMD) sampling method for a few examples where PLOP sampling is insufficient are also reported. The results reported indicate that the OPLS-AA/AGBNP effective potential is suitable for high-resolution modeling of proteins in the final stages of homology modeling and/or protein crystallographic refinement.
OPLS-AA全原子力场和解析广义玻恩加非极性（AGBNP）隐式溶剂模型，结合基于蛋白质局部优化程序（PLOP）的扭转角构象搜索协议，被证明在预测一系列低序列同一性的蛋白质中57个9残基环和35个13残基环的天然构象方面是有效的。AGBNP中实现的新型非极性溶剂化自由能估计器通过旨在减少离子配对发生的校正项得到增强，这对于实现最佳预测准确性很重要。报告了基于晶体环境计算的先前开发的基于PLOP的构象搜索方案的扩展版本，这些版本适用于在没有晶体环境的情况下应用于环同源性建模。我们的结果表明，一般来说，环主链构象不受晶体堆积的强烈影响。还报告了温度复制交换分子动力学（T-REMD）采样方法在一些PLOP采样不足的例子中的应用。报告的结果表明，OPLS-AA/AGBNP有效势适用于同源性建模和/或蛋白质晶体学精修最后阶段的蛋白质高分辨率建模。
