Constant pH molecular dynamics in generalized Born implicit solvent

J Comput Chem. 2004 Dec;25(16):2038-48. doi: 10.1002/jcc.20139.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Hydrogen-Ion Concentration
  • Models, Molecular*
  • Monte Carlo Method*
  • Muramidase / chemistry*
  • Solvents
  • Thermodynamics

Substances

  • Solvents
  • hen egg lysozyme
  • Muramidase