Industry Talk Astex

Event Date/s: Thursday 30 June 2022, 14:00 - 15:30


Title: Do proteins ever strain drug-like ligands?


Location: Online (after you register you will receive a Zoom link), note the webinar starts at 2pm UK time


Speaker: John Liebeschuetz, Astex


Registration: free, deadline 28 June 2022, click here to register



It is usually accepted that minimising ligand strain is useful if one wishes to design potent ligand-efficient drugs. Yet there is not yet full consensus how much strain energy can be acceptably accommodated in a drug-like ligand. This talk will look at single-point and dynamics-based methods for calculating strain energies from protein-ligand complexes and discuss the considerable difficulties inherent in generating accurate values.  An alternative approach will be presented whereby we compare torsional ligand geometries in highly resolved protein-ligand complexes,  with similar substructures in the Cambridge Structural Database (1). This study led to the conclusion that we may need to reassess the commonly held idea of a single principle binding pose.

  1. The Good, the Bad and the Twisted Revisited: An Analysis of ligand geometry in Highly Resolved protein-Ligand X-Ray Structures. J. W.Liebeschuetz, J. Med. Chem. 2021, 64, 11, 7533-7543