BAGIM is an active community of Boston area scientists bringing together people from diverse fields of modeling and informatics to impact life and health sciences. BAGIM strives to create a forum for great scientific discussions covering a wide range of topics including data management, visualization, computational chemistry, drug discovery, protein structure, molecular modeling, structure-based drug design, data mining, software tools, and the sharing of goals and experiences. Our community is made up of participants from academia, government, and industry whose goal is to engage in the discussion of science involving a synthesis of theory and technology. Discussions sponsored by BAGIM are targeted to the needs and interests of informatics scientists, computational chemists, medicinal chemists, and statisticians. BAGIM also provides opportunities for networking within these disciplines as well as an arena for the dissemination of information of specific interest to the membership.

Wednesday, January 25, 2017

BAGIM Event: Dr. Matthew Segall Wed March 1 at Millennium Takeda

Dr. Matthew Segall, CEO of Optibrium, will present "Predicting Routes, Sites and Products of Metabolism by Cytochrome P450 " on Wednesday March 1, starting at 6pm at the Millennium Takeda Oncology building at 35 Landsdowne St in Cambridge.  Refreshments and networking will follow at Asgard, 350 Massachusetts Ave in Cambridge.

Please RSVP to help us plan for this event.


In this presentation, we will describe recent developments to a method for predicting Cytochrome P450 (P450) metabolism that combines quantum mechanical (QM) simulations to estimate the reactivity of potential sites of metabolism on a compound with a ligand-based approach to account for the effects of orientation and steric constraints due to the binding pockets of different P450 isoforms (DOI: 10.1021/acs.jcim.6b00233). These new developments include modelling reaction pathways for epoxidation and developing models for an extended range of P450 isoforms. The resulting models achieve accuracies of 85-90% on independent test sets.

The metabolites resulting from oxidation at each potential site of metabolism can also be predicted, to guide experimental metabolite identification and highlight potentially active, reactive or toxic metabolites for further investigation. However, as the regioselectivity of metabolism may be different for each isoform, to predict the profile of metabolites that are likely to be formed, it is also necessary to identify which isoforms will be responsible for the metabolism of a compound. We will describe the latest results of our research to develop an accurate ‘WhichP450’ model, which can be coupled with isoform-specific regioselectivity models to generate a ranked list of expected metabolites.

Biography for Matthew Segall

Matt is CEO of Optibrium. He has a Master of Science in computation from the University of Oxford and a Ph.D. in theoretical physics from the University of Cambridge. As Associate Director at Camitro (UK), ArQule Inc. and then Inpharmatica, he led a team developing predictive ADME models and state-of-the-art intuitive decision-support and visualization tools for drug discovery. In January 2006, he became responsible for management of Inpharmatica's ADME business, including experimental ADME services and the StarDrop software platform. Following acquisition of Inpharmatica, Matt became Senior Director responsible for BioFocus DPI's ADMET division and in 2009 led a management buyout of the StarDrop business to found Optibrium, which develops software for small molecule design, optimisation and data analysis. Matt has published over 30 peer-reviewed papers and book chapters on computational chemistry, cheminformatics and drug discovery.

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