Williams Sarah L, de Oliveira César Augusto F, McCammon J Andrew
Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, California 92093-0365, Center for Theoretical Biological Physics, University of California San Diego, La Jolla, California 92093, Howard Hughes Medical Institute, University of California San Diego, La Jolla, California 92093-0365, Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0365.
J Chem Theory Comput. 2010 Feb 9;6(2):560-568. doi: 10.1021/ct9005294. Epub 2010 Jan 14.
An extension of the constant pH method originally implemented by Mongan et al. (J. Comput. Chem.2004, 25, 2038-2048) is proposed in this study. This adapted version of the method couples the constant pH methodology with the enhanced sampling technique of accelerated molecular dynamics, in an attempt to overcome the sampling issues encountered with current standard constant pH molecular dynamics methods. Although good results were reported by Mongan et al. on application of the standard method to the hen egg-white lysozyme (HEWL) system, residues which possess strong interactions with neighboring groups tend to converge slowly, resulting in the reported inconsistencies for predicted pK(a) values, as highlighted by the authors. The application of the coupled method described in this study to the HEWL system displays improvements over the standard version of the method, with the improved sampling leading to faster convergence and producing pK(a) values in closer agreement to those obtained experimentally for the more slowly converging residues.
本研究提出了对最初由蒙根等人（《计算化学杂志》，2004年，第25卷，2038 - 2048页）实施的恒定pH方法的扩展。该方法的改进版本将恒定pH方法与加速分子动力学的增强采样技术相结合，试图克服当前标准恒定pH分子动力学方法所遇到的采样问题。尽管蒙根等人报道了将标准方法应用于鸡蛋清溶菌酶（HEWL）系统时取得了良好结果，但与相邻基团具有强相互作用的残基往往收敛缓慢，导致预测的pK(a)值出现作者所强调的不一致情况。本研究中描述的耦合方法应用于HEWL系统时，相较于该方法的标准版本有改进，改进后的采样导致更快收敛，并产生与实验获得的结果更接近的pK(a)值，适用于收敛较慢的残基。
