title: PBSA_E: A PBSA-Based Free Energy Estimator for Protein-Ligand Binding Affinity.
abstract: Improving the accuracy of scoring functions for estimating protein-ligand binding affinity is of significant interest as well as practical utility in drug discovery. In this work, PBSA_E, a new free energy estimator based on the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) descriptors, has been developed. This free energy estimator was optimized using high-quality experimental data from a training set consisting of 145 protein-ligand complexes. The method was validated on two separate test sets containing 121 and 130 complexes. Comparison of the binding affinities predicted using the present method with those obtained using three popular scoring functions, i.e., GlideXP, GlideSP, and SYBYL_F, demonstrated that the PBSA_E method is more accurate. This new energy estimator requires a MM/PBSA calculation of the protein-ligand binding energy for a single complex configuration, which is typically obtained by optimizing the crystal structure. The present study shows that PBSA_E has the potential to become a robust tool for more reliable estimation of protein-ligand binding affinity in structure-based drug design.
authors.affiliation: Department of Physics, State Key Laboratory of Precision Spectroscopy, College of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Physics, State Key Laboratory of Precision Spectroscopy, College of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Physics, State Key Laboratory of Precision Spectroscopy, College of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062, China.|NYU-ECNU Center for Computational Chemistry at NYU Shanghai , Shanghai 200062, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Lujia
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physics, State Key Laboratory of Precision Spectroscopy, College of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062, China.|NYU-ECNU Center for Computational Chemistry at NYU Shanghai , Shanghai 200062, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Physics, State Key Laboratory of Precision Spectroscopy, College of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062, China.|NYU-ECNU Center for Computational Chemistry at NYU Shanghai , Shanghai 200062, China.|Department of Chemistry, New York University , New York, New York 10003, United States.|Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan , Shanxi 030006, China.
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins