TCB Seminar

Alchemical free energy calculations for stability and affinity predictions

Professor Bert de Groot
Computational Biomolecular Dynamics Group
Max Planck Institute for Biophysical Chemistry
Goettingen, Germany

Tuesday, October 20, 2020
11:00 am
Zoom webinar link

Abstract

Alchemical free energies form a powerful computational tool for the accurate prediction of stability changes due to mutation or relative ligand-receptor binding affinities. A non-equilibrium protocol facilitated by the PMX software will be presented for the efficient computation of such alchemical free energy changes, making use of thermodynamic cycles. A large-scale mutation scan will be presented on thermostability estimates due to point mutations in proteins, reaching an unprecedented accuracy thanks to a consensus force field approach. In addition, the affect of nucleic acid mutations on the affinity of protein-DNA complex will be presented. Finally, a protocol will be introduced for the efficient and accurate computation of relative affinities between receptors and drug-like ligands, for a set of 482 ligans pairs binding to 13 different receptors.