Dear all,
We are pleased to announce that our next industrial speaker will be Nicolas
Foloppe from Vernalis. The talk will be on 26 August 2021 at 2pm British time
(registration is free but required by 24 August 2021). Details and registration
can be found at https://www.ccpbiosim.ac.uk/binding2021.
Title: Characterising the unbound state of drug-like compounds: implications
for molecular recognition
Abstract: The unbound state of drug compounds is important to better understand
their binding to proteins, including conformational preorganization and the
intramolecular reorganization energy of compounds upon binding (ΔEReorg). These
questions were addressed with molecular dynamics (MD) simulations of diverse
compounds, unbound or complexed to their protein target. Analysis of those
systems involved observations regarding their electrostatics.
The unbound compounds simulated with MD were compared to conformers
generated with implicit generalized Born (GB) aqueous solvation models. The
notion of conformational pre-organization for binding was investigated by
comparing the simulated compounds to their bioactive X-ray structure. The study
yielded low to moderate values of ΔEReorg for most, but not all, compounds. For
three particularly polar compounds, ΔEReorg was substantial (≥ 15 kcal/mol).
Those large ΔEReorg values may be interpreted as a redistribution of
electrostatic interactions upon binding.
Best wishes,
Sarah
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