Constant pH molecular dynamics in generalized Born implicit solvent

2004/10/12 by John Mongan, David A. Case, J. Andrew McCammon · 6 citations
Biochemistry, Genetics and Molecular Biology · Materials Science · Physics and Astronomy · #Enzyme Structure and Function #Protein Structure and Dynamics #Spectroscopy and Quantum Chemical Studies

paper · doi:10.1002/jcc.20139

openalex publication_date 2004/10/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27

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.

Citations

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