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Limiting assumptions in structure-based design: binding entropy

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Abstract

In order to deal with the complexity of biological systems at the atomic level, limiting assumptions are often made which do not reflect the reality of the system under study. One example is the assumption that the entropy of binding of the macromolecule is not influenced significantly by the different ligands. Recent experimental data on ligands binding to HIV-1 protease challenge this assumption.

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Acknowledgments

Many have contributed to my limited understanding of the limitations of what we have collectively attempted. Certainly, David Barry, Denise Beusen, Heinz Bosshard, Dick Cramer, Richard Dammkoehler, Wayne Hubbell, Martin Karplus, Charlie Molnar, Phil Needleman, Tudor Oprea, Jay Ponder, Jake Schaefer, Harold Scheraga, Andy Vinter, Svante Wold, and many others (too numerous to mention) have generously pointed out critical mistakes in my thinking along my path to humility. My scientific gratitude to the EPR community whose work on HIV-1 protease has so clearly elucidated the problem. My thanks as well to the modeling community for indulging both my passion and my naivety. If one really knew how difficult was the journey, would one have taken that first step?

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  1. Department of Biochemistry and Molecular Biophysics, Washington University, St. Louis, MO, USA

    Garland R. Marshall

  2. Department of Biomedical Engineering, Washington University, St. Louis, MO, USA

    Garland R. Marshall

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  1. Garland R. Marshall
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Correspondence to Garland R. Marshall.

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Marshall, G.R. Limiting assumptions in structure-based design: binding entropy. J Comput Aided Mol Des 26, 3–8 (2012). https://doi.org/10.1007/s10822-011-9494-1

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  • DOI: https://doi.org/10.1007/s10822-011-9494-1

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