Dr. Elizabeth Villar, formerly advised by BMERC faculty members Prof. Sandor Vajda and Prof. Adrian Whitty, will be leading an elevator pitch workshop and discussing effective ways to talk about science. This workshop is part of the event series hosted by BU-BEST, a program with the initiative to enhance biomedical career development curricula for Ph.Ds and postdocs.
Paul C. D. Hawkins, Ph.D.
Head of Scientific Solutions
Title: When thinking is just not enough: Computation for drug discovery at 10^0 to 10^10.
Abstract: This talk will highlight two applications of computation in modern drug discovery: similarity searching at scales up to and beyond 10^10 and ligand design using a rigorous understanding of both entropic and enthalpic contributions to conformational stability.
When: Wednesday, April 25th, 12 pm
Where: ERB room 203, 44 Cummington Mall
The BMERC will be having an open house on March 12th from 5 to 6:15 PM in ERB 203. Please join us for a poster session and refreshments.
The BMERC Seminar Series will be starting up soon for the Spring semester. This semester we are hosting leaders in both industry and academia. Our guest speakers from industry represent two companies that are focused on computational drug discovery. OpenEye Scientific Software will give a presentation on the ways that chemistry, biology and engineering labs can utilize their software with a free academic license. The chief scientific officer of Silicon Therapeutics, Woody Sherman, PhD, will also give a presentation on the latest methods of integrated computational drug discovery for creating novel small molecule therapeutics for difficult to target proteins.
The talks will be on select Wednesdays from 12:00 PM to 1:30 PM in ERB 203. Lunch will be provided. Dates are TBD.
When: Thursday, June 22, 12 pm
Where: ENG room 203, 44 Cummington Street
Title: Exploiting secondary binding pockets in aminergic GPCRs
Speaker: Dr. Gyorgy Keseru, Medicinal Chemistry Research Group, Hungarian Academy of Science, Budapest, Hungary
Abstract: Fragment based drug discovery (FBDD) employs growing and linking strategies for optimization. Structural information on G-protein coupled receptors (GPCRs) made FBDD available on this class of targets, however, most reported programs applied a growing strategy starting from orthosteric fragment binders. We developed a sequential docking methodology to support the identification of primary (orthosteric) and secondary site binders and linking of these fragment hits. Predicting the binding mode of multiple fragments bound to a single target we assessed the sampling and scoring accuracy for the first and second site binders in self- and cross-docking situations. The prospective validation of this approach was performed on dopamine receptors using the human dopamine D3 receptor crystal structure and a human dopamine D2 receptor homology model. Two focused fragment libraries were docked in the primary and secondary binding sites, and best fragment combinations were enumerated. Similar top scoring fragments were found for the primary site, while secondary site fragments were predicted to convey selectivity. A set of linked compounds created from the best scored primary and secondary site binders were synthesized from which we identified a number of D3 favoring compounds including one with 200-fold D3 selectivity. The structural assessment of the subtype selectivity of the compounds allowed us to identify further compounds with high affinity and improved selectivity. Now we are extending the methodology to further aminergic GPCR targets.
When: Thursday, December 8, 10:30 am
Where: ENG room 203, 44 Cummington Street
Title: Promiscuity in regulatory proteins such as PD-1 hinder their druggability
Speaker: Prof. Carlos J. Camacho
Department of Computational and Systems Biology
University of Pittsburgh
Abstract: Many regulatory proteins use structural flexibility to bind specifically to multiple partners. Although conformational selection and induced fit offer alternative pathways to rationalize multi-ligand binding, in practice we lack a structural understanding of how nature designs a flexible binding interface to select some ligands, but not others. Using molecular dynamics simulations (MDS) to identify the molecular interactions responsible for this “selective promiscuity”, I will show that promiscuity can be triggered by ligand-