Meng Yilin, Roitberg Adrian E
Department of Chemistry and Quantum Theory Project. University of Florida Gainesville, FL 32611-8435.
J Chem Theory Comput. 2010 Apr 13;6(4):1401-1412. doi: 10.1021/ct900676b.
A constant pH replica exchange molecular dynamics (REMD) method is proposed and implemented to improve coupled protonation and conformational state sampling. By mixing conformational sampling at constant pH (with discrete protonation states) with a temperature ladder, this method avoids conformational trapping. Our method was tested and applied to seven different biological systems. The constant pH REMD not only predicted pKa correctly for small, model compounds but also converged faster than constant pH molecular dynamics (MD). We further tested our constant pH REMD on a heptapeptide from ovomucoid third domain (OMTKY3). Although constant pH REMD and MD produced very close pKa values, the constant pH REMD showed its advantage in the efficiency of conformational and protonation state samplings.
为了改进耦合质子化和构象状态采样，提出并实现了一种恒定pH值的复制交换分子动力学（REMD）方法。通过将恒定pH值下的构象采样（具有离散质子化状态）与温度梯度相结合，该方法避免了构象捕获。我们的方法在七个不同的生物系统上进行了测试和应用。恒定pH值的REMD不仅能正确预测小分子模型化合物的pKa值，而且比恒定pH值分子动力学（MD）收敛得更快。我们进一步在来自卵类粘蛋白第三结构域（OMTKY3）的七肽上测试了我们的恒定pH值REMD。尽管恒定pH值的REMD和MD产生的pKa值非常接近，但恒定pH值的REMD在构象和质子化状态采样效率方面显示出其优势。
