title: Optimizing the affinity and specificity of ligand binding with the inclusion of solvation effect.
abstract: Solvation effect is an important factor for protein-ligand binding in aqueous water. Previous scoring function of protein-ligand interactions rarely incorporates the solvation model into the quantification of protein-ligand interactions, mainly due to the immense computational cost, especially in the structure-based virtual screening, and nontransferable application of independently optimized atomic solvation parameters. In order to overcome these barriers, we effectively combine knowledge-based atom-pair potentials and the atomic solvation energy of charge-independent implicit solvent model in the optimization of binding affinity and specificity. The resulting scoring functions with optimized atomic solvation parameters is named as specificity and affinity with solvation effect (SPA-SE). The performance of SPA-SE is evaluated and compared to 20 other scoring functions, as well as SPA. The comparative results show that SPA-SE outperforms all other scoring functions in binding affinity prediction and "native" pose identification. Our optimization validates that solvation effect is an important regulator to the stability and specificity of protein-ligand binding. The development strategy of SPA-SE sets an example for other scoring function to account for the solvation effect in biomolecular recognitions.
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences Changchun, Jilin, 130022, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences Changchun, Jilin, 130022, China.|Department of Chemistry & Physics, State University of New York at Stony Brook, Stony Brook, New York, 11794-3400, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D001667:Binding, Competitive; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D009010:Monte Carlo Method; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results; D012996:Solutions / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D012996:Solutions; D012997:Solvents
keywords: SPA; binding affinity; binding specificity; protein-ligand binding; scoring function; solvation energy