title: A strategy for reducing gross errors in the generalized Born models of implicit solvation.
abstract: The "canonical" generalized Born (GB) formula [C. Still, A. Tempczyk, R. C. Hawley, and T. Hendrickson, J. Am. Chem. Soc. 112, 6127 (1990)] is known to provide accurate estimates for total electrostatic solvation energies ΔG(el) of biomolecules if the corresponding effective Born radii are accurate. Here we show that even if the effective Born radii are perfectly accurate, the canonical formula still exhibits significant number of gross errors (errors larger than 2k(B)T relative to numerical Poisson equation reference) in pairwise interactions between individual atomic charges. Analysis of exact analytical solutions of the Poisson equation (PE) for several idealized nonspherical geometries reveals two distinct spatial modes of the PE solution; these modes are also found in realistic biomolecular shapes. The canonical GB Green function misses one of two modes seen in the exact PE solution, which explains the observed gross errors. To address the problem and reduce gross errors of the GB formalism, we have used exact PE solutions for idealized nonspherical geometries to suggest an alternative analytical Green function to replace the canonical GB formula. The proposed functional form is mathematically nearly as simple as the original, but depends not only on the effective Born radii but also on their gradients, which allows for better representation of details of nonspherical molecular shapes. In particular, the proposed functional form captures both modes of the PE solution seen in nonspherical geometries. Tests on realistic biomolecular structures ranging from small peptides to medium size proteins show that the proposed functional form reduces gross pairwise errors in all cases, with the amount of reduction varying from more than an order of magnitude for small structures to a factor of 2 for the largest ones.
authors.affiliation: Department of Computer Science, 2050 Torgersen Hall, Virginia Tech, Blacksburg, Virginia 24061, USA. alexey@cs.vt.edu
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Onufriev
authors.forename: Grigori
authors.initials: G
authors.lastname: Sigalov
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry; D012995:Solubility; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D010455:Peptides; D011506:Proteins; D012996:Solutions; D012997:Solvents