title: Quantifying the stabilizing energy of the intraprotein hydrogen bond due to local mutation.
abstract: MD simulation of the WW domain of PIN based on a dynamically adjusted polarized protein-specific force field from quantum fragment calculations is carried out in both wild and VAL22ALA mutant states. The result shows that the geometry of the Arg14-TYR23 hydrogen bond is conserved upon mutation of VAL22 to ALA. However, the electrostatic energy of this hydrogen bond in the mutant is found to be 0.6 kcal/mol weaker than in the wild state, in close agreement with the experimentally measured upper limit of 1.2 kcal/mol. Analysis shows that the weakened energy of this hydrogen bond in the mutant is due to its dynamically changed polarization resulting from an altered local electrostatic environment near the hydrogen bond which becomes more exposed to the solvent than in the wild.
authors.affiliation: State Key Laboratory of Precision Spectroscopy, Department of Physics, East China Normal University, Shanghai 200062, China. chicago.ji@gmail.com
authors.forename: Chang G
authors.initials: CG
authors.lastname: Ji
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D056445:Cytoplasmic Dyneins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009154:Mutation; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: C427758:DYNLL1 protein, human; D056445:Cytoplasmic Dyneins