Recent development of titratable coions has paved the way for realizing all-atom molecular dynamics at constant pH. To further improve physical realism, here we describe a technique in which proton titration of the solute is directly coupled to the interconversion between water and hydroxide or hydronium. We test the new method in replica-exchange continuous constant pH molecular dynamics simulations of three proteins, HP36, BBL, and HEWL. The calculated pKa values based on 10-ns sampling per replica have the average absolute and root-mean-square errors of 0.7 and 0.9 pH units, respectively. Introducing titratable water in molecular dynamics offers a means to model proton exchange between solute and solvent, thus opening a door to gaining new insights into the intricate details of biological phenomena involving proton translocation. © 2013 Biophysical Society.
Chen, W., Wallace, J. A., Yue, Z., & Shen, J. K. (2013). Introducing titratable water to all-atom molecular dynamics at constant pH. Biophysical Journal, 105(4). https://doi.org/10.1016/j.bpj.2013.06.036