Physics based simulations in early-stage drug discovery
DRA lecture held by Dr. Willem Jespers, Assistant professor, Leiden Academic Centre for Drug Research (LACDR), Leiden University, The Netherlands
Free Energy Perturbation (FEP) is one of the most accurate computational approaches to estimate the affinity of small molecules for a biological target. Its application in pharmaceutical drug discovery has been steadily increasing over the last decade. This is largely caused by an increase in throughput of the method driven by advances in hardware and the increase in efficient workflows. To this extent, Dr. Jespers recently developed QligFEP, a python package written around the software package Q, which is different to most methods in that it applies spherical boundary conditions to represent the binding site. Together with a dual topology representation of the ligand coordinates, this approach offers a computationally efficient and versatile package, which was recently benchmarked against 8 pharmaceutical targets using the Open Force Field. One caveat of FEP is that the efficiency of the method is still dependent on sufficient phase-space overlap between the molecular entities, typically obtained by introducing unphysical intermediates between two molecules of interest. Dr. Jespers will present a method to automatically design physical intermediates that, if carefully applied, could 1) overcome the problem of phase-space overlap and 2) potentially provide additional structure activity relationships (SAR) by connecting physical intermediates whilst simultaneously reducing the sampling time for unphysical intermediates.
The lecture is organised on behalf of the graduate programme in pharmaceutical sciences, Drug Research Academy, by Research Consultant Kasper Harpsøe and Postdoc Icaro Simon, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen.
The DRA lecture is free of charge and open for attendance by all interested parties. It is not necessary to pre-register.