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-acetyltrypto...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS 1993-09, Vol.90 (18), p.8402-8406
Hauptverfasser:	Miyamoto, Shuichi, Kollman, Peter A.
Format:	Artikel
Sprache:	eng
Schlagworte:	Aqueous solutions Atoms Bacterial Proteins - metabolism Binding sites Biological and medical sciences Biotin - metabolism Calorimetry Chymotrypsin - metabolism Electrostatics Free energy Fundamental and applied biological sciences. Psychology Hydrogen bonds Interactions. Associations Intermolecular phenomena Ligands Methane Models, Molecular Molecular biophysics Molecules Protein Binding Protein Conformation Proteins Proteins - chemistry Proteins - metabolism Streptavidin Tryptophan - analogs & derivatives Tryptophan - metabolism Water
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Beschreibung
Zusammenfassung:	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/α-chymotrypsin. This difference in free energy of association is due to van der Waals/dispersion effects in the nearly ideally preformed cavity that streptavidin presents to biotin, which involves four tryptophan residues.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.90.18.8402