Dear all,

Our next online Industry Talk will be on Thursday 30 June 2022 at 2pm UK time. 
The speaker is John Liebeschuetz from Astex and the title is "Do proteins ever 
strain drug-like ligands?".

Details and the registration link can be found at 
www.ccpbiosim.ac.uk/astex2022<http://www.ccpbiosim.ac.uk/astex2022>.


Abstract: 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

Best wishes,
Sarah



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