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Ranking ligand binding affinities with avidin: a molecular dynamics‐based interaction energy study
Author(s) -
Wang Jian,
Dixon Richard,
Kollman Peter A.
Publication year - 1999
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19990101)34:1<69::aid-prot6>3.0.co;2-c
Subject(s) - molecular dynamics , binding energy , binding affinities , affinities , avidin , chemistry , thermodynamic integration , computational chemistry , binding site , ligand (biochemistry) , work (physics) , interaction energy , energy (signal processing) , chemical physics , flexibility (engineering) , thermodynamics , molecule , stereochemistry , physics , biotin , atomic physics , biochemistry , mathematics , organic chemistry , receptor , statistics , quantum mechanics
The binding of 14 biotin analogues to avidin is examined to evaluate the viability of calculating binding free energy based on molecular dynamics (MD) trajectories. Two approaches were investigated in this work. The first one uses the linear interaction energy approximation, while the other approach utilizes the interaction free energy. The results obtained from these two methods were found to correlate well with the experimental binding free energy data for 10 out of 14 ligands. For the other four ligands, both methods overestimate their binding strength by more than 7 kcal/mol. Free energy calculations using the thermodynamic integration method are employed to understand this overestimation. The effect of protein flexibility on binding free energy calculation and the effect of charged or neutral ligands on the calculated results are discussed. MD simulations are shown to be able to provide insight into the interactions occurring in the active site and the origins of variations in binding free energy. Proteins 1999;34:69–81. © 1999 Wiley‐Liss, Inc.