Enhancing Conformation and Protonation State Sampling of Hen Egg White Lysozyme Using pH Replica Exchange Molecular Dynamics
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- 作者：Jason M. Swails ; Adrian E. Roitberg
- 刊名：Journal of Chemical Theory and Computation
- 出版年：2012
- 出版时间：November 13, 2012
- 年：2012
- 卷：8
- 期：11
- 页码：4393-4404
- 全文大小：672K
- 年卷期：v.8,no.11(November 13, 2012)
- ISSN：1549-9626
文摘
We evaluate the efficiency of the pH replica exchange molecular dynamics (pH-REMD) method proposed by Itoh et al. (Proteins2011, 79, 3420鈥?436) by using it to predict the pKa values of the titratable residues in hen egg white lysozyme (HEWL). pKa values predicted using pH-REMD converge significantly faster than those calculated using constant pH molecular dynamics (CpHMD). Furthermore, increasing the frequency between exchange attempts in pH-REMD simulations improves protonation and conformational state sampling. By enabling the simulation to sample both conformational and protonation states more rapidly, pH-REMD simulations provide valuable insight into the pH-dependence of HEWL that the CpHMD simulations failed to capture. We present an efficient and highly scalable implementation of pH-REMD as an attractive enhancement to traditional CpHMD methods.