METHOD FOR DETERMINING PROTEIN PROTONATION STATE BASED ON CONSTANT-PH MOLECULAR DYNAMICS SIMULATION

摘要

Provided is a method based on constant-pH molecular dynamics simulation for determining the state of protein protonation, comprising calculation of the ΔG_{elec, ref} of a reference compound; configuring a reasonable initial protonation state on the basis of a simulated target pH value; performing constant-pH molecular dynamics simulation to restrict the positions of protein main-chain atoms; setting amino acid residues having protonation proportions greater than 99% or less than 1% as "no titration", titrating other amino acid residues, and performing conventional constant-pH molecular dynamics simulation; setting amino acid residues having protonation proportions greater than 90% or less than 10% as "no titration", titrating other amino acid residues, and performing constant-pH molecular dynamics simulation at pH-0.5, pH-0.2, pH, pH+0.2, pH+0.5 respectively; fitting to a Hill equation to obtain a final pKa, the protonation status being determined by means of the pKa.