On October 31, 2018, with the invitation of Prof. Gao Jiali, Prof. Alex MacKerell from University of Maryland visited our school and gave a wonderful lecture titled “Can CADD Drive GPCR Drug Design? Rapid Estimation of Relative Binding Affinities Based on Pre-computed Ensembles” in D building ladder classroom, teachers and students of our school actively participated in the academic discussions and exchanged ideas.

       Firstly, Professor Alex MacKerell introduced the basics of computer-aided drug design. Rapid, accurate estimation of relative ligand affinities offers the potential to allow computational methods to direct drug design and development. Towards this goal MacKerell Group have developed two methods based on pre-computed ensembles: Site Identification by Ligand Competitive Saturation (SILCS) and Single-Step Free Energy Perturbation (SSFEP). SILCS is based on computational functional group affinity mapping (FragMaps) of proteins using oscillating μ_ex Grand Canonical Monte Carlo/Molecular Dynamics (GCMC/MD) simulations that take into account contributions from protein desolvation, functional group desolvation, protein flexibility as well as functional group-protein interactions. In SSFEP a lead compound-protein complex is subjected to MD simulations from which an ensemble of ligand-protein conformations is obtained. Similar calculations are done on the ligand in solution. Free energy differences associated with small chemical modifications of the lead compound may then be evaluated using the free energy perturbation formulation in the context of single step perturbations.Secondly, Professor Alex MacKerel introduced the application of the above two methods in GPCR drug design.

       After the speech, professors and students of our school discussed with Prof. Alex MacKerel actively. Then, Prof. Alex MacKerel had a lunch meeting with students. In the symposium, Prof. Alex MacKerel answered the students some problems about the science research, and also introduced the scientific life in the USA. (Written by Lu Zhengchang)

Brief introduction of speaker:

Professor Alexander MacKerell

Grollman-Glick Professor of Pharmaceutical Sciences, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland

Director, Computer-Aided Drug Design Center, School of Pharmacy, University of Maryland