Summary
Free energy derivatives, which were first used to analyze the sensitivity and the convergence of free energy calculations, have recently been proposed for use in analog design. In this article, we review the published applications of free energy derivatives to analog design, discuss the possible reasons for the success and failure of such applications, and describe our recent study on an alternative use of free energy derivatives in analog design. It is too early to definitively evaluate the usefulness of the free energy derivative method to yield valuable insights into analog design. Our recent study suggests that free energy derivatives hold promise in evaluating possible different binding sites for a given ligand and suggesting the sites of a ligand that are not suitable for further structural modifications.
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On sabbatical leave from: Neurochemistry Research, Mayo Foundation for Medical Education and Research, 4500 San Pablo Road, Jacksonville, FL 32224, U.S.A.
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Pang, YP., Kollman, P.A. Applications of free energy derivatives to analog design. Perspectives in Drug Discovery and Design 3, 106–122 (1995). https://doi.org/10.1007/BF02174469
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DOI: https://doi.org/10.1007/BF02174469