pH is critical for chemical and biological processes. To simulate pH-dependent processes, the continuous constant pH molecular dynamics (CpHMD) method has been developed. The CpHMD method was initially based on the generalized Born implicit-solvent model, which introduces unphysical artifacts. To avoid the drawback of the implicit-solvent model, the CpHMD method was recently extended to all-atom explicit-solvent simulations. For the all-atom CpHMD, titratable co-ions are used to balance charges of titratable groups varying in simulations. However, varying charges of co-ions such as sodium and cloride are unphysical. To replace the unphysical co-ions, we developed titratable water models, which enable interconversion between water and hydroxide/hydronium (Figure 1A). We tested the titratable water models on titration of three proteins, HP36, BBL, and HEWL. The calculated pka's are in good agreement with experiment with average unsigned and root-man-square errors less than one pH unit (Figure 1B). In addition, coupling of titratable water to titratable groups of solute mimics proton exchange between solute and solvent, openning up opportunities to study proton transfer involved in many biological systems such as proton channels. 

Titratable water models for all-atom constant pH molecular dynamics

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.