Calculation of Absolute Protein-Ligand Binding Affinity Using Path and Endpoint Approaches

• Published in: Biophysical journal Vol. 90; no. 3; pp. 864 - 877
• Main Authors: Lee, Michael S., Olson, Mark A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2006; Biophysical Society
• Subjects: Binding Sites; Biophysical Theory and Modeling; Biophysics - methods; Butanones - chemistry; Carrier Proteins; Comparative analysis; Computer Simulation; Crystallography, X-Ray; Entropy; Hot Temperature; Hydrogen Bonding; Kinetics; Ligands; Models, Molecular; Molecular Structure; Molecules; Protein Binding; Protein Conformation; Proteins; Proteins - chemistry; Solvents; Tacrolimus - chemistry; Thermodynamics

A comparative analysis is provided of rigorous and approximate methods for calculating absolute binding affinities of two protein-ligand complexes: the FKBP protein bound with small molecules 4-hydroxy-2-butanone and FK506. Our rigorous approach is an umbrella sampling technique where a potential of...