title: Role of the protein side-chain fluctuations on the strength of pair-wise electrostatic interactions: comparing experimental with computed pK(a)s.
abstract: The effect of the protein side-chain fluctuations on the strength of electrostatic interactions was studied. The effect was modeled on 7 different crystal structures on the same enzyme as well as on 20 molecular dynamics snapshot structures. It was shown that the side-chain flexibility affects predominantly the magnitude of the strong pair-wise interactions, that is, the pair-wise interaction among ion pairs, and practically does not affect the interactions with the rest of the protein. This was used to suggest a correction function that should be applied to the original pair-wise electrostatic interaction to mimic the effects of the fluctuations. The procedure is applied on three ion pairs identified in lysozyme. It was shown that sampling different side-chain rotamers and modifying the strength of the pair-wise interaction energies makes calculated pK(a)s less sensitive to the fluctuations of the structure and improves the prediction accuracy.
authors.affiliation: Howard Hughes Medical Institute and Biochemistry Department, Columbia University, New York, New York 10032, USA. ea388@columbia.edu
authors.forename: Emil
authors.initials: E
authors.lastname: Alexov
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D007477:Ions; D007700:Kinetics; D008958:Models, Molecular; D009038:Motion; D009113:Muramidase / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D000596:Amino Acids; D007477:Ions; D011506:Proteins; C421864:hen egg lysozyme; D009113:Muramidase