时间：2018年10月26日（周五）   上午10：00- 11：00
　　Time: October 26, 2018   10:00-11:00AM
　　地点：西湖大学云栖校区5号楼一楼学术报告厅
　　Venue: Lecture Hall, 1stFloor, Build 5, Yunqi Campus
　　主持人:生命科学学院 黄晶博士
　　Host: Dr. Jin Huang, School of Life Sciences
　　主讲嘉宾：

　　ProfessorAlexander 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
　　
　　Alex MacKerell received an A.S. in Biology from Gloucester County College, a B.S. in Chemistry from the University of Hawaii and a Ph.D. in Biochemistry from Rutgers University.  Subsequent training involved postdoctoral fellowships in the Department of Medical Biophysics, Karolinska Intitutet, Stockholm, Sweden in experimental and theoretical biophysics and in the Department of Chemistry, Harvard University in theoretical chemistry.  MacKerell is currently theGrollman-Glick Professor of Pharmaceutical Sciences in the School of Pharmacy, University of Maryland, Baltimore and the Director of the University of Maryland Computer-Aided Drug Design Center.  MacKerell is also Co-founder and Chief Scientific Officer of SilcsBio LLC.  Research interests include the development of theoretical chemistry methods, with emphasis on empirical force fields, including the CHARMM additive and Drude polarizable force fields, structure-function studies of proteins, carbohydrates and nucleic acids, and drug design and development.
　　讲座摘要：
　　Rapid, accurate estimation of relative ligand affinities offers the potential to allow computational methods to direct drug design and development.  Towards this goal we 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 oscillatingμex 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.  The method can be applied to a range of macromolecules including those with deep or full inaccessible binding pockets such GPCRs and nuclear receptors. Grid Free Energy (GFE) FragMaps obtained from the GCMC/MD simulations may be used both qualitatively and quantitatively to direct ligand design.  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. Both SILCS and SSFEP allow for rapid scoring of 1000s of transformations on a daily time frame offering the potential to identify synthetically accessible ligands thereby facilitating decisions concerning compounds for synthesis and testing. An overview of the SSFEP and SILCS methodologies will be presented along with application of the methods in the context of lead compound identification and optimization in the context of GPCRs.
　　联系人：科技合作部  沈老师   shenxiaolian@westlake.edu.cn