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The slow but steady rise of binding free energy calculations in drug discovery

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Abstract

Binding free energy calculations are increasingly used in drug discovery research to predict protein-ligand binding affinities and to prioritize candidate drug molecules accordingly. It has taken decades of collective effort to transform this academic concept into a technology adopted by the pharmaceutical and biotech industry. Having personally witnessed and taken part in this transformation, here I recount the (incomplete) list of problems that had to be solved to make this computational tool practical and suggest areas of future development.

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Acknowledgements

I wish to acknowledge my colleagues, especially Justin Gullingsrud, Ross Lippert, Michael Bergdorf, and Sean Baxter, for their critical contributions to the BFE functionality in DESMOND. I thank Woody Sherman and Alexander Tropsha for thoughtful suggestions to this writing and Yunxing (Stella) Li for her help in preparing Fig. 1.

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    Huafeng Xu

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Huafeng Xu is a shareholder of Stingthera, which is conducting clinical trials of the STING agonist described in reference [105]. Huafeng Xu is the sole author of this paper.

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Supplementary file1 (XLSX 49 kb). Number of publications in medicinal chemistry and drug discovery journals reporting BFE applications

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Xu, H. The slow but steady rise of binding free energy calculations in drug discovery. J Comput Aided Mol Des 37, 67–74 (2023). https://doi.org/10.1007/s10822-022-00494-x

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