Enabling structure-based drug discovery utilizing predicted models

Edward B Miller; Howook Hwang; Mee Shelley; Andrew Placzek; João P G L M Rodrigues; Robert K Suto; Lingle Wang; Karen Akinsanya; Robert Abel

doi:10.1016/j.cell.2023.12.034

Enabling structure-based drug discovery utilizing predicted models

Cell. 2024 Feb 1;187(3):521-525. doi: 10.1016/j.cell.2023.12.034.

Authors

Edward B Miller¹, Howook Hwang², Mee Shelley³, Andrew Placzek³, João P G L M Rodrigues², Robert K Suto⁴, Lingle Wang², Karen Akinsanya², Robert Abel²

Affiliations

¹ Schrödinger New York, 1540 Broadway, 24th Floor, New York, NY 10036, USA. Electronic address: ed.miller@schrodinger.com.
² Schrödinger New York, 1540 Broadway, 24th Floor, New York, NY 10036, USA.
³ Schrödinger Portland, 101 SW Main Street, Suite 1300, Portland, OR 97204, USA.
⁴ Schrödinger Framingham, 200 Staples Drive, Suite 210, Framingham, MA 01702, USA.

PMID: 38306979
DOI: 10.1016/j.cell.2023.12.034

Abstract

High-quality predicted structures enable structure-based approaches to an expanding number of drug discovery programs. We propose that by utilizing free energy perturbation (FEP), predicted structures can be confidently employed to achieve drug design goals. We use structure-based modeling of hERG inhibition to illustrate this value of FEP.

MeSH terms

Drug Design*
Drug Discovery*
Entropy
Thermodynamics