Constant pH molecular dynamics in generalized Born implicit solvent

John Mongan, David A. Case, J. Andrew McCammon

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393 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2038-2048
Number of pages11
JournalJournal of Computational Chemistry
Issue number16
StatePublished - Dec 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Computational Mathematics


  • Constant pH molecular dynamics
  • Generalized Born
  • Lysozyme
  • Monte Carlo
  • pKa prediction


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