There has been a substantial amount of recent interest in treating pH as an explicit component in molecular simulations, similar to temperature or pressure. This is because pH influences the protonation states of macromolecules, which in turn affects their behavior. In particular, in systems such as cytochrome c oxidase, the photoactive yellow protein, and ATP synthase, conformational changes have been linked to protonation state changes of key residues. Therefore, it is important to be able to sample structural and protonation changes sufficiently in order to determine free energy barriers. Recently, we developed new methods, EDS-HREM and 2D-EDS-HREM, which combine Enveloping Distribution Sampling with Hamiltonian Replica Exchange, to perform constant pH simulations in explicit solvent. The utility of these methods has been recently demonstrated for predicting the pH-dependent binding behavior of host-guest complexes. This talk will discuss continued work that involves improving the performance of these new methods and applying them to different molecular systems.

Advances in constant pH molecular simulation with the EDS-HREM and 2D-EDS-HREM methods

251st National Meeting (2016)

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