Parametrization of calcium binding site in proteins and molecular dynamics simulation on phospholipase A2

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AbstractThe empirical energy parameters for a calcium ion and its ligands in proteins were determined within a pairwise additive framework. The interaction energies of Ca2+‐water, Ca2+‐peptide group and Ca2+‐carboxyl group systems were calculated using the ab initio molecular orbital method with basis sets of double zeta quality including polarization or diffuse functions. The resulting potential energy surfaces served as references for the determination of the nonbonded parameters in the empirical energy function. The nonadditive corrections for the Ca2+‐ligand pair potentials are incorporated implicitly in the nonbonded paremeters by treating three‐body (1:2 complex) or seven‐body (1:6 complex) systems in reference calculations. Ligand polarizations induced by Ca2+ are estimated from the partial atomic charges of two‐body (1:1 complex) systems. The charge sets were determined by scaling so as to reproduce the reference potential energy surfaces. The newly determined parameter set was used in a stochastic boundary molecular dynamics simulation of phospholipase A2. The solvated structure of the Ca2+‐binding site obtained from an X‐ray crystallographic study is well reproduced by the parameter set.