title: A residue-pairwise generalized born scheme suitable for protein design calculations.
abstract: We describe an efficient generalized Born (GB) approximation for proteins, in which the interaction energy between two amino acids depends on the whole protein structure, but can be accurately computed from residue-pairwise information. Two results make the scheme pairwise. First, an accurate expression exists for the interaction energy between two residues R and R' that depends on the product B = BRBR' of their residue Born solvation radii. Second, this expression is accurately fitted by a parabolic function of B; the (three) fitting coefficients depend only on the pair RR', not on its environment. In effect, the quantity B captures all the information that is relevant about the pair's dielectric environment. The method is tested with calculations on several hundred structures of the proteins trpcage, BPTI, ubiqutin, and thoredoxin. It yields solvation energies in better agreement with Poisson calculations than a traditional GB formulation. We also compute the effect of the protein/solvent environment on the interactions between pairs of charged residues in the active site of the enzyme aspartyl-tRNA synthetase. Our method captures this effect as accurately as traditional GB. Because it is residue-pairwise, the method can be incorporated into efficient protocols for rotamer placement and computational protein design.
authors.affiliation: Department of Physics, University of Cyprus, PO20537, CY1678, Nicosia, Cyprus. archonti@ucy.ac.cy
authors.forename: Georgios
authors.initials: G
authors.lastname: Archontis
authors.forename: Thomas
authors.initials: T
authors.lastname: Simonson
mesh_terms: D001226:Aspartate-tRNA Ligase / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D008956:Models, Chemical; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D055672:Static Electricity
chemical_list: D011506:Proteins; D012997:Solvents; D001226:Aspartate-tRNA Ligase