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.
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
John
J
Mongan
David A
DA
Case
J Andrew
JA
McCammon
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