BAGIM Event: Dr. Todd Martinez, Wednesday May 3rd at Vertex Pharmaceuticals, starting at 5:30pm

Dr. Todd J. Martinez, of Stanford University, will present "Quantum Chemistry and Ab Initio Molecular Dynamics on Graphical Processing Units" on Wednesday, May 3rd, 2017, at Vertex Pharmaceuticals.  Dr. Martinez will present at 7pm, but networking and refreshments will precede the talk starting at 5:30pm.

Please RSVP with your full name to help us plan for the event and to help speed security check in.

Abstract: Solution of the electronic structure problem (often known as “quantum chemistry”) is a critical step in much of chemical simulation. For example, quantum chemistry is required to fit parameters for empirical force fields and also for ab initio molecular dynamics approaches which eschew force fields altogether. The recent introduction of stream processors such as graphical processing units (GPUs) promises to accelerate quantum chemistry calculations. We provide an overview of the differences between GPUs and conventional CPUs and discuss how quantum chemistry algorithms can be redesigned to use GPUs effectively. We show that accelerations of up to three orders of magnitude can be achieved (relative to conventional CPU implementations) by exploiting GPUs with redesigned algorithms. Several applications enabled by these advances are discussed, including an assessment of the size of QM regions needed to achieve convergence in QM/MM methods. Finally, we discuss the ab initio nanoreactor, which uses GPU-enabled ab initio molecular dynamics to discover reaction networks. We present the overall concept of the nanoreactor and some first applications to complex reaction networks in combustion and prebiotic chemistry.

BAGIM is sponsored by Dassault Systemes, DNASTAR, LabAnswer, OpenEye Scientific, Schrodinger, Silicon Therapeutics, Acellera, Acpharis, Cambridge Crystallographic Data Centre, Chemical Computing Group, Dotmatics, Cresset, Cyrus Biotechnology, Optibrium, Team Arrayo, and Scilligence

BAGIM Event: Dr. Meir Glick, Thursday April 13 at Le Meridien in Cambridge, starting at 6pm

Dr. Meir Glick, the Director of Informatics at Merck Research Laboratories, will present "A forward-looking strategy on how can chemistry and informatics enable biology" on Thursday, April 13th, starting at 6pm at Le Méridien Cambridge-MIT, 20 Sidney Street in Cambridge. Food, drinks, and networking will follow at Asgard, 350 Massachusetts Ave in Cambridge.

Please RSVP at to help us plan for this event.

Abstract

This presentation describes how integration of screening, chemical synthesis and informatics can enable target identification and validation. More specifically, design of high quality molecular probes that perturb novel targets and phenotypes, creation of the most biologically relevant assays systems, progressing the right perturbagen into in vivo studies and eventually transforming the organization from data creators into decision makers.

Biography for Meir Glick

Dr. Glick is the Director of Informatics where he is responsible for the vision, strategy and delivery for a world class group that influences all of Merck Research. Before joining Merck in 2015 Dr. Glick was the head of the in silico Lead Discovery at the Novartis Institutes for BioMedical Research where he worked since 2003. He was a trained as a postdoc in the area of computational chemistry in the University of Oxford and received his PhD in computational chemistry from the Hebrew University of Jerusalem. Dr. Glick is the author of over 60 scientific papers in peer reviewed journals, patents and book chapters (https://scholar.google.com/citations?user=fwxyVs8AAAAJ&hl=en)

BAGIM is sponsored by Dassault Systemes, DNASTAR, LabAnswer, OpenEye Scientific, Schrodinger, Silicon Therapeutics, Acellera, Acpharis, Cambridge Crystallographic Data Centre, Chemical Computing Group, Cresset, Cyrus Biotechnology, Optibrium, Team Arrayo, and Scilligence

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.

Abstract

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.

BAGIM Event: Dr. John Conway & panel discussion on Cloud Computing Tuesday 2/7, at Vertex

Dr. John Conway of LabAnswer will present a lecture concerning cloud computing strategies for discovery research starting at 6pmon Tuesday, February 7th in the 9th floor multipurpose room of building 1 at Vertex Pharmaceuticals at 50 Northern Avenue, Boston. A panel discussion with Q/A on cloud computing will follow with Chris Waller from Merck, Dave Johnson from Moderna, and Steve Litster from Novartis. Networking will follow at approximately 7:30pm, more details TBD. 



Please RSVP  with your real first and last names to speed the sign in process at Vertex. You will find additional information there about the contents of the presentation.


Abstract: Many discovery research organizations struggle with their research informatics environments. Startups and new ventures may have these problems for reasons different than more established discovery research organizations. One observation for startups is the lack of resources or time to focus on strategic thinking and planning because researchers and supporting IT are consumed by tactical priorities and decisions. Defining criteria for decision making and future direction is imperative to a solid scientific data strategy and now with the cloud as an option; an infrastructure strategy. Newer organizations might choose a strict cloud environment where more established organizations will start to migrate towards cloud and will most likely result in a hybrid (on-premise/cloud) environment. From a scientific software vendor perspective, multi-tenant cloud solutions/platforms have the ability to solve and reduce many costly processes, interactions, and problems. From a client perspective, the cloud affords the opportunities of plug and play, reduced internal IT footprint, more efficient collaboration and faster adoption. This BAGIM event is to discuss and generate observations in the discovery research industry with respects to cloud informatics and computational approaches and solutions and to generate a report for the BAGIM community based on the resulting observations and discussions. Topics to be discussed include adoption, implementation, successes, failure, and the future.


BAGIM is sponsored by Dassault Systemes, DNASTAR, LabAnswer, Schrodinger, Silicon Therapeutics, Acellera, Acpharis, Cambridge Crystallographic Data Centre, Chemical Computing Group, Cresset, Cyrus Biotechnology, Dotmatics, Optibrium, Team Arrayo, and Scilligence

BAGIM Event: Dr. John Burke Thursday January 19 at The Broad Institute

Dr. John Burke, CEO of Applied BioMath, will present "Quantitative Modeling and Simulation Approaches: Driving Critical Decisions from Research through Clinical Trials" at the Broad Institute at 415 Main Street in Cambridge on Thursday, January 19th.  The talk will begin at 6pm in the auditorium and be followed by refreshments and networking at Meadhall at 4 Cambridge Center starting around 7pm.   Please RSVP for the meeting. 

Abstract: Quantitative Systems Pharmacology (QSP) is a mathematical modeling and engineering approach to translational medicine that aims to quantitatively integrate knowledge about therapeutics with an understanding of its mechanism of action in the context of human disease mechanisms. The goal of QSP modeling is “to understand, in a precise, predictive manner, how drugs modulate cellular networks in space and time and how they impact human pathophysiology [1].” In doing so, QSP approaches de-risk projects, accelerate the development of best in class therapeutics, and reduce late stage attrition rates. This results is helping industry save money, accelerate timelines, and make better therapeutics, ultimately improving patients’ lives. In the five years since the NIH QSP Working Group met last on this topic, progress has been made to advance this science and to integrate QSP approaches in the drug discovery and development process in industry. Here several case studies will be shown that highlights examples of QSP efforts that have accelerated the discovery and development of best-in-class therapeutics, and impacted critical decisions, in the continuum from preclinical exploration to clinical research. Examples include: providing biological understanding, impacts on new target proposals, lead generation, clinical candidate selection, IND support, and clinical trial go/no go decisions from industry.

1. Sorger, PK, et al. Quantitative and Systems Pharmacology in the Post-genomic Era: New Approaches to Discovering Drugs and Understanding Therapeutic Mechanisms. An NIH White Paper, QSP Workshop Group R. Ward, Editor. 2011.

Dr. Burke is CEO, President and Co-founder of Applied BioMath. He earned his PhD in Applied Mathematics from Arizona State University, completed a senior postdoctoral fellowship in Biological Engineering at Massachusetts Institute of Technology, and was Co-Scientific Director of the Cell Decision Process Center at Harvard Medical School, a NIH Center of Excellence. While at MIT and HMS he provided systems consulting support for large and small pharma and biotechs (e.g., AstraZeneca, Pfizer, Momenta), and software companies (e.g., Jacobian and MathWorks). Next he was at Merrimack Pharmaceuticals as a Senior Mathematical Biologist. He then was Global Head of Systems Biology and Pharmacology at Boehringer Ingelheim (BI). He was responsible for starting, implementing, scaling, and managing the worldwide strategy, portfolio, and efforts of BI’s systems initiatives. In a span of five years his group supported over 120 milestone transitions and major decisions from new target stage, lead generation, clinical candidate selection, through clinical trial support. Project indications and platforms included Oncology, Metabolic Disease, CNS, Cardiovascular, Respiratory, Infectious Disease, Inflammation and Immunology for large molecules, fixed dose combinations, ADC, and cell therapies. He is presently an Adjunct Professor at University of Massachusetts, Lowell, developing a QSP course at Harvard Medical School to be taught in the Spring of 2017, an industry advisor for the NIH/NCATS “Translational Center of Tissue Chip Technologies” and the DARPA - MIT Human on a Chip Grant, and an advisor to the Mathematics Department, University of Massachusetts, Lowell

BAGIM is sponsored by Dassault Systemes, DNASTAR, LabAnswer, Schrodinger, Silicon Therapeutics, Acellera, Acpharis, Cambridge Crystallographic Data Centre, Chemical Computing Group, Cresset, Cyrus Biotechnology, Dotmatics, Optibrium, and Scilligence,

BAGIM Event: Dr. Georgia McGaughey Monday December 5 at Millennium Takeda in Cambridge

Dr. Georgia McGaughey of Vertex Pharmaceuticals will present "Shaping Computational Chemistry Tools for Impact: Application of Experimental and Theoretical Methods for Orexin Antagonists" at the Millennium Takeda Oncology building at 35 Landsdowne Street in Cambridge, MA on Monday, December 5th. The presentation will begin at 6pm followed by refreshments and networking at Asgard, 350 Massachusetts Ave. Adding your full name to your RSVP  will speed security registration at Takeda.

BAGIM is sponsored by Scilligence, Silicon Therapeutics, Acellera, Cyrus Biotechnology, DNASTAR, OpenEye Scientific Software, Schrodinger, Chemical Computing Group, ARIAD Pharmaceuticals, Vertex Pharmaceuticals, the Cambridge Crystallographic Data Centre, Optibrium, Dassault Systemes, Dotmatics, LabAnswer, and ChemAxon.

BAGIM Event: Panel Discussion Exploring Careers in Computational Chemistry and Cheminformatics at Moderna November 10th

Interested in pursuing a career in computational chemistry or cheminformatics? Join us for a panel discussion by young career scientists in industry, ranging from big pharma to startups. Learn tips and tricks for successful interviewing, networking, and job hunting. Hear what it's like making the transition from academia to industry and what it's like working in the field.   A BAGIM networking event at Cambridge Brewing Company will follow the panel discussion at 7:15pm.

·  5:30-6pm -- Drinks and food

·  6-7pm -- Career panel aimed at graduate students and postdocs considering careers in comp chem

o Panelists include

§ Dr. Rebecca Swett (Vertex)

Dr. Swett graduated from Wayne State University in Detroit, where she applied molecular dynamics to the development and optimization of covalent inhibitors of the Clostridium Difficile toxins, and developed methods to apply interference in protein-protein recognition as a mechanism of inhibition, leading to her first patent. Additionally, she developed software connect genotypes to phenotypes by gene region of interest, in a hypothesis-driven manner and validated the results with simulations and in vitro experiments. She then completed a postdoc at Novartis with an academic mentor at Stanford. Here she worked on applying ultra-fine print molecular dynamics to the use of solvation in lead optimization, application of Markov State Modeling to the identification of targetable metastable protein states for the development of flu treatments, and developed predictive models to discriminate between ligand effects on correlated protein motions in high throughput MD. She currently is at Vertex Pharmaceuticals where she uses an array of ligand and structure based methods, as well as predictive modeling and molecular dynamics, to pursue treatments for Cystic Fibrosis and other targets.

§ Dr. Levi Pierce (Relay Therapeutics) 

Levi is a computer engineer who has worked in several startups spanning the fields of genomics and pharmaceutical drug design.  The combination of these two fields will usher in personalized medicine.  While at Schrodinger Inc, he was a key developer of a computational tool (Free Energy Perturbation, FEP) used to accurately predicting binding affinity of drugs in lead optimization.  He then worked at Human Longevity Inc using a variant of FEP to study drug sensitivity observed in cancer mutations obtained from next generation sequencing.  Currently he is at Relay Therapeutics where he is leveraging computational tools to develop drugs for mutations observed in patient populations.  

§ Dr. Christine Hajdin (Novartis)

Currently, Christine is an investigator in the CADD (Computer Assisted Drug Discovery) group at Novartis. Here she utilizes a mix of machine learning, informatics, programming and structure-based design to identify potential target/compound interactions.  Prior to coming to Novartis, she worked at Explorys (now IBM Watson Health) as a data scientist modeling cost reduction and risk aversion strategies.  She obtained her Ph.D. from UNC Chapel Hill in biological chemistry and undergraduate degrees in math and biochemistry from Miami University.

Moderated by Dr. Finith Jernigan, III (Silicon Therapeutics). 

Dr. Jernigan is a co-founder and chief technology officer of Silicon Therapeutics and was instrumental in developing the underlying technology INSITE. Prior to founding Silicon Therapeutics, Dr. Jernigan was at Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School, where his focused on identification of tool compounds using novel in silico screening approaches for targets identified by BIDMC investigators. This work, performed in the labs of Drs. Sun and Chaikof, led to the creation Silicon Therapeutics’ proprietary drug discovery platform, INSITE. Prior to that, Dr. Jernigan earned his Ph.D. in organic chemistry at the University of North Carolina at Chapel Hill in the lab of Dr. David S. Lawrence. His work at the University of North Carolina focused on the synthesis and development of fluorescent sensors of kinases and the proteasome. This work led to multiple publications in top chemistry journals, including Journal of the American Chemical Society and Angewandte Chemie International Edition. Dr. Jernigan holds a B.S. in Biochemistry from Salisbury University, a Ph.D. in Organic Chemistry from the University of North Carolina at Chapel Hill, and was a postdoctoral fellow at BIDMC/Harvard Medical School.