biostudies-literatureWu YNational Institute of General Medical SciencesNIGMS NIH HHS5535-5549https://www.ebi.ac.uk/biostudies/studies/S-EPMC8684595biostudies-literatureUnknown61(11)The binding of small-molecule ligands to protein or nucleic acid targets is important to numerous biological processes. Accurate prediction of the binding modes between a ligand and a macromolecule is of fundamental importance in structure-based structure-function exploration. When multiple ligands with different sizes are docked to a target receptor, it is reasonable to assume that the residues in the binding pocket may adopt alternative conformations upon interacting with the different ligands. In addition, it has been suggested that the entropic contribution to binding can be important. However, only a few attempts to include the side chain conformational entropy upon binding within the application of flexible receptor docking methodology exist. Here, we propose a new physics-based scorJournal of chemical information and modelingFlexible CDOCKER: Hybrid Searching Algorithm and Scoring Function with Side Chain Conformational Entropy.PMC8684595GM037554R01 GM103695R35 GM130587GM130587R01 GM037554GM107233R01 GM107233Brooks CLWu YfalseFlexible CDOCKER: Hybrid Searching Algorithm and Scoring Function with Side Chain Conformational Entropy.The binding of small-molecule ligands to protein or nucleic acid targets is important to numerous biological processes. Accurate prediction of the binding modes between a ligand and a macromolecule is of fundamental importance in structure-based structure-function exploration. When multiple ligands with different sizes are docked to a target receptor, it is reasonable to assume that the residues in the binding pocket may adopt alternative conformations upon interacting with the different ligands. In addition, it has been suggested that the entropic contribution to binding can be important. However, only a few attempts to include the side chain conformational entropy upon binding within the application of flexible receptor docking methodology exist. Here, we propose a new physics-based scor2021-01-01T00:00:00Z2021 Nov2026-05-09T19:30:06.019Z2025-04-19T22:47:59.31ZS-EPMC86845953470475410.1021/acs.jcim.1c01078