Abstract:
:We explore the question of what are the best ligands for macromolecular targets. A survey of experimental data on a large number of the strongest-binding ligands indicates that the free energy of binding increases with the number of nonhydrogen atoms with an initial slope of approximately -1.5 kcal/mol (1 cal = 4.18 J) per atom. For ligands that contain more than 15 nonhydrogen atoms, the free energy of binding increases very little with relative molecular mass. This nonlinearity is largely ascribed to nonthermodynamic factors. An analysis of the dominant interactions suggests that van der Waals interactions and hydrophobic effects provide a reasonable basis for understanding binding affinities across the entire set of ligands. Interesting outliers that bind unusually strongly on a per atom basis include metal ions, covalently attached ligands, and a few well known complexes such as biotin-avidin.
journal_name
Proc Natl Acad Sci U S Aauthors
Kuntz ID,Chen K,Sharp KA,Kollman PAdoi
10.1073/pnas.96.18.9997keywords:
subject
Has Abstractpub_date
1999-08-31 00:00:00pages
9997-10002issue
18eissn
0027-8424issn
1091-6490journal_volume
96pub_type
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