What determines the strength of noncovalent association of ligands to proteins in aqueous solution?
Free energy perturbation methods using molecular dynamics have been used to calculate the absolute free energy of association of two ligand-protein complexes. The calculations reproduce the significantly more negative free energy of association of biotin to streptavidin, compared to N-L-acetyltryptophanamide/alpha-chymotrypsin. This difference in free energy of association is due to van der Waals/dispersion effects in the nearly ideally performed cavity that streptavidin presents to biotin, which involves four tryptophan residues.
Miyamoto
S
S
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143.
Kollman
P A
PA
D001426:Bacterial Proteins / Q000378:metabolism*; D001710:Biotin / Q000378:metabolism; D002151:Calorimetry; D002918:Chymotrypsin / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D019809:Streptavidin; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism
D001426:Bacterial Proteins; D008024:Ligands; D011506:Proteins; C016952:N-acetyltryptophanamide; D001710:Biotin; D014364:Tryptophan; D019809:Streptavidin; D002918:Chymotrypsin