Constant pH molecular dynamics in generalized Born implicit solvent.
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.
Mongan
John
J
The Center for Theoretical Biological Physics, University of California at San Diego, 9500 Gilman Dr., La Jolla, California 92093-0365, USA. jmongan@mccammon.ucsd.edu
Case
David A
DA
McCammon
J Andrew
JA
D000465:Algorithms; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D009010:Monte Carlo Method; D009113:Muramidase / Q000737:chemistry*; D012997:Solvents; D013816:Thermodynamics
D012997:Solvents; C421864:hen egg lysozyme; D009113:Muramidase