Prediction of protein loop conformations using the AGBNP implicit solvent model and torsion angle sampling
Prediction of protein loop conformations using the AGBNP implicit solvent model and torsion angle sampling
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DOI：
10.1021/ct800051k
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发表时间：
2008-05-01
影响因子：
5.5
通讯作者：
Levy, Ronald M.
中科院分区：
文献类型：
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作者：
Felts, Anthony K.;Gallicchio, Emilio;Levy, Ronald M.
OPLS-AA全原子力场和分析性的概括性出生加非极性（AGBNP）隐式溶剂模型，以及基于蛋白质局部优化程序（PLOP）的扭转角构象搜索协议（PLOP），可在预测具有低序列同一性的一系列多样化蛋白质的57个9-占用物和35个13个残留环的天然构象。在AGBNP中实现的新型非极性溶剂能估计器，其旨在减少离子配对发生的校正术语对实现最佳预测准确性很重要。据报道，基于晶体环境中计算的先前开发的基于PLOP的构象搜索方案的扩展版本适合在没有晶体环境的情况下应用循环同源性建模。我们的结果表明，一般而言，环路主链构象不受晶体堆积的强烈影响。还报道了一些案例的应用，在一些示例中，还报告了温度复制品交换分子动力学（T-REMD）采样方法的应用。结果报道的结果表明，OPLSAA/AGBNP有效潜力适用于同源性建模和/或蛋白质晶体学改进的最后阶段中蛋白质的高分辨率建模。
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 OPLSAA/AGBNP effective potential is suitable for high-resolution modeling of proteins in the final stages of homology modeling and/or protein crystallographic refinement.