title: In silico binding free energy predictability with π-π interaction energy-augmented scoring function: benzimidazole Raf inhibitors as a case study.
abstract: The ability to estimate binding affinities of ligands precisely is of paramount importance in designing drugs. Docking programs are used primarily to predict the binding mode of ligands to receptors. However, current scoring functions as used in docking programs are not reliable enough to predict binding affinities of ligands without any further calculations. In the present study, we investigate the usefulness of adding π-π interaction energies between ring groups of residues and ligands to the scoring function for docking. It is found that such addition helps ranking ligand activities more correctly. LMP2 calculation is used to measure π-π interaction energies between ring groups. The result of this simple addition shows possibility of π-π interaction generalization in scoring functions.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Chung
authors.forename: Seung Joo
authors.initials: SJ
authors.lastname: Cho
authors.forename: Art E
authors.initials: AE
authors.lastname: Cho
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Hah
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry*; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods*; D004583:Electrons; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D048490:raf Kinases / Q000037:antagonists & inhibitors*
chemical_list: D001562:Benzimidazoles; D008024:Ligands; D047428:Protein Kinase Inhibitors; D048490:raf Kinases