Thermodynamic resolution: How do errors in modeled protein structures affect binding affinity predictions?

摘要: The present study addresses the effect of structural distortion, caused by protein modeling errors, on calculated binding affinities toward small molecules. to a total 300 distorted structures based five different protein–ligand complexes were evaluated establish broadly applicable relationship between errors in structure and affinities. Relatively accurate models (less than 2 A RMSD within site) demonstrate 14.78 (±7.5)% deviation affinity from that using corresponding crystal structure. For 2–3 A, 3–4 >4 site, error increases 20.8 (±5.98), 22.79 (±11.3), 29.43 (±11.47)%, respectively. results described here may be used combination with other tools evaluate utility modeled for drug development or ligand-binding studies. Proteins 2010. © 2010 Wiley-Liss, Inc.