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.

Thursday, September 14, 2017

BAGIM Event: Dr. Heidi Koldsø at Moderna in Cambridge, Thursday Oct 19th

Dr. Heidi Koldsø from D. E. Shaw Research will present "Permeation, gating, and modulation of the TRPA1 channel in long-timescale molecular dynamics simulations"on Thursday, October 19, 2017.  The talk will be held at Moderna Therapeutics at 200 Technology Square in Cambridge, starting at 6pm.  Please plan to arrive ten to fifteen minutes before the start.  Networking and refreshments will follow the talk at Meadhall, 4 Cambridge Center. 

TRPA1, a member of the transient receptor potential (TRP) ion channel superfamily, is a nonspecific cation channel activated by natural chemicals found in, for instance, mustard, oregano, and cinnamon.  TRPA1 has recently appeared as a promising drug target in pain and inflammatory diseases.  Structure-based design efforts for this protein are problematic, however, due to the lack of molecular details of relevant channel functional states and of channel activation. 

To address this problem, we have studied TRPA1 channel functional states and channel activation using long-timescale, all-atom molecular dynamics simulations enabled by special-purpose hardware.  Specifically, we simulated inward and outward ionic currents, which helped us identify possible key structural determinants of channel gating.  We also studied modulation of the open and conducting channel by performing simulations of free binding of the TRPA1 inhibitor A-967079 to TRPA1.  Intriguingly, A-967079 was observed to bind in a location previously hypothesized to be a binding site.  Our observations suggest that this site may indeed be a target for development of new allosteric modulators, an avenue we intend to explore in the future.

Heidi Koldsø is a member of the technical team at D. E. Shaw Research, a company that develops specialized hardware and software for basic and applied computational biochemical research. She holds a Ph.D. in chemistry from Aarhus University in Denmark, as well as a M.Sc. and B.Sc. in Medicinal Chemistry, also from Aarhus University. After her Ph.D., she was a postdoctoral researcher at the Department of Biochemistry, University of Oxford. At D. E. Shaw Research, she applies molecular dynamics simulations to study biological systems, with a focus on ion channels.

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

Monday, September 11, 2017

BAGIM Event: Panel on Cloud Computing for Molecular Modeling at NIBR in Cambridge, Monday September 11, 2017

A panel of industry experts will present a discussion on Cloud Computing for Molecular Modeling in the auditorium at NIBR at 250 Mass Avenue in Cambridge, starting at 6pm, following refreshments at 5:30pm. Further networking time with refreshments will follow the discussion. Panel members include:  

• Lucas Nivon, Ph.D. (discussion leader)
Co-founder and CEO, Cyrus Biotechnology 
• Pat Lorton, Ph.D. (panelist)
Chief Technology Officer, Schrodinger
• Essam Metwally, Ph.D. (panelist)
Senior Scientist, Chemical Computing Group
• Craig Bruce, Ph.D. (panelist)
Scientific Software Development Manager, OpenEye Scientific

Molecular Modeling on the Cloud: Implementing complex workflows for all users

Many major advances have been made in the last 10 years in small molecule and protein modeling and design, including the design of novel protein folds and protein-binding activity into inert scaffolds. All of these have required very large amounts of computing and complex workflows with sensitive benchmarking and expert configuration. This complexity, sensitivity and large infrastructure requirements have in many cases limited these tools to very few use cases in an academic environment with access to very large shared compute resources. We propose that the public cloud provides an opportunity to circumvent infrastructure limitations while simultaneously reducing complexity and increasing accessibility.

Here we examine the previously existing infrastructure used to run these types of calculations. We consider the design requirements for a value-focused research organization in a cloud implementation of molecular modeling and design, such as maintenance cost/time, reliability, speed to answers, and correctness of answers. Then we propose various architectural instantiations of a “cloud” modeling suite of software while considering best practices in software-as-a-service tools from other fields (such as email). Finally, we outline one general solution to a cloud architecture that emphasizes these requirements and reduces user complexity. Simplification to users requires shifting complexity to cloud infrastructure and increased software development time.

We focus on one case study of a scientific workflow implementation, detailing architectural/workflow aspects and the scientific benchmarking required.

Special thanks to NIBR for hosting, especially Lewis Whitehead and Erica Gauthier, ACS COMP for sponsoring refreshments

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