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Constant pH molecular dynamics in generalized Born implicit solvent.

John Mongan·David A Case·J Andrew McCammon
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Abstract

A new method is proposed for constant pH molecular dynamics (MD), employing generalized Born (GB) electrostatics. Protonation states are modeled with different charge sets, and titrating residues sample a Boltzmann distribution of protonation states as the simulation progresses, using Monte Carlo sampling based on GB-derived energies. The method is applied to four different crystal structures of hen egg-white lysozyme (HEWL). pK(a) predictions derived from the simulations have root-mean-square (RMS) error of 0.82 relative to experimental values. Similarity of results between the four crystal structures shows the method to be independent of starting crystal structure; this is in contrast to most electrostatics-only models. A strong correlation between conformation and protonation state is noted and quantitatively analyzed, emphasizing the importance of sampling protonation states in conjunction with dynamics.

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AlgorithmsHydrogen-Ion ConcentrationModels, MolecularMonte Carlo MethodMuramidaseSolventsThermodynamicsJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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John Mongan, David A Case, J Andrew McCammon. 2004. Constant pH molecular dynamics in generalized Born implicit solvent.. https://doi.org/10.1002/jcc.20139

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