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Comparative Analysis of Electrostatic Models for Ligand Docking

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Autor(es):
Sartori, Geraldo Rodrigues [1] ; Nascimento, Alessandro S. [1]
Número total de Autores: 2
Afiliação do(s) autor(es):
[1] Univ Sao Paub, Sao Carlos Inst Phys, Sao Carlos, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN MOLECULAR BIOSCIENCES; v. 6, JUL 3 2019.
Citações Web of Science: 0
Resumo

The precise modeling of molecular interactions remains an important goal among molecular modeling techniques. Some of the challenges in the field include the precise definition of a Hamiltonian for biomolecular systems, together with precise parameters derived from Molecular Mechanics Force Fields, for example. The problem is even more challenging when interaction energies from different species are computed, such as the interaction energy involving a ligand and a protein, given that small differences must be computed from large energies. Here we evaluated the effects of the electrostatic model for ligand binding energy evaluation in the context of ligand docking. For this purpose, a classical Coulomb potential with distance-dependent dielectrics was compared with a Poisson-Boltzmann (PB) model for electrostatic potential computation, based on DelPhi calculations. We found that, although the electrostatic energies were highly correlated for the Coulomb and PB models, the ligand pose and the enrichment of actual ligands against decoy compounds, were improved when binding energies were computed using PB as compared to the Coulomb model. We observed that the electrostatic energies computed with the Coulomb model were, on average, ten times larger than the energies computed with the PB model, suggesting a strong overestimation of the polar interactions in the Coulomb model. We also found that a slightly smoothed Lennard-Jones potential combined with the PB model resulted in a good compromise between ligand sampling and energetic scoring. (AU)

Processo FAPESP: 15/13684-0 - Estudos estruturais e funcionais de enzimas que participam na síntese e degradação de carboidratos complexos
Beneficiário:Igor Polikarpov
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 17/18173-0 - Mecanismos envolvidos em resistência a antibióticos: parede de ácidos teicóicos e biofilmes como alvos moleculares
Beneficiário:Alessandro Silva Nascimento
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 15/26722-8 - Drug discovery contra doenças infecciosas humanos
Beneficiário:Carsten Wrenger
Linha de fomento: Auxílio à Pesquisa - Temático