Abstract: A potential energy surface scanning method and system for the analysis of molecular conformational space includes: judge whether the molecule has adjacent dihedral angles. If there are adjacent dihedral angles, judge whether the adjacent dihedral angles are coupled by QM calculations. If they are judged not to be coupled, then perform one-dimensional potential energy scanning. If judged to be coupled, then perform MM coupling judgment. If the MM calculations determine that the adjacent dihedral angles are not coupled, a one-dimensional potential energy surface scan is performed. If the MM calculation judges that the adjacent dihedral angles are coupled, calculate the coverage of the extreme points on the two-dimensional potential energy surface by the combination of extreme points obtained by scanning the individual one-dimensional potential energy surfaces of the two dihedral angles according to the MM scanning result. If the coverage is good, then perform one-dimensional potential energy surface scanning.

Abstract: A potential energy surface scanning method and system for the analysis of molecular conformational space includes: judge whether the molecule has adjacent dihedral angles. If there are adjacent dihedral angles, judge whether the adjacent dihedral angles are coupled by QM calculations. If they are judged not to be coupled, then perform one-dimensional potential energy scanning. If judged to be coupled, then perform MM coupling judgment. If the MM calculations determine that the adjacent dihedral angles are not coupled, a one-dimensional potential energy surface scan is performed. If the MM calculation judges that the adjacent dihedral angles are coupled, calculate the coverage of the extreme points on the two-dimensional potential energy surface by the combination of extreme points obtained by scanning the individual one-dimensional potential energy surfaces of the two dihedral angles according to the MM scanning result. If the coverage is good, then perform one-dimensional potential energy surface scanning.

Abstract: A method for determining protonation states of a protein on the basis of constant-pH molecular dynamics simulation includes: calculating ?Gelec,ref of a reference compound; setting reasonable initial protonation states according to a simulation target pH value; performing constant-pH molecular dynamics simulation, and restricting positions of protein main chain atoms; setting amino acid residues with a protonation state proportion of higher than 99% or lower than 1% to be not titrated and other amino acid residues to be titrated, performing conventional constant-pH molecular dynamics simulation; setting amino acid residues with a protonation state proportion of higher than 90% or lower than 10% to be not titrated and other amino acid residues to be titrated, performing constant-pH molecular dynamics simulation under conditions of pH?0.5, pH?0.2, pH, pH+0.2, pH+0.5, respectively; performing Hill equation fitting to obtain a final pKa, wherein the protonation state can be determined by pKa.