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.

Monday, April 1, 2019

BAGIM Event: Mike Bower

Please join us on April 25th at 6:00 pm at Verizon Alley (10 Ware St, Cambridge) for a talk by Mike Bower entitled: PXR Mitigation and Structure-Based Design

Upregulation of CYP450 3A4 via activation of the pregnane X receptor (PXR) is an active and growing concern for pharmaceutical discovery and development, as it can lead to unpredictable and potentially dangerous drug-drug interactions.  I will introduce a novel molecular descriptor, Smallest Maximum Interatomic Distance (SMID), which correlates with PXR activation.  I will also present a method for using the descriptor to guide chemists in modifying their lead compounds to decrease PXR activation. 

The presenter, Mike Bower, received a BS in Chemistry from the University of Delaware. During undergrad, Mike had his first computational chemistry job as an intern at DuPont Merck Pharmaceutical Co (28 years ago). Mike received a PhD in Pharmaceutical Chemistry from the University of California at San Francisco, where he worked in Fred Cohen’s lab on homology modeling and sidechain modeling using his program, SCWRL.  Since then, Mike has worked at Chiron pharmaceuticals, SmithKline Beecham/GlaxoSmithKline, Incyte Corporation, and now Vertex Pharmaceuticals.  He spent four years as the communication/social media officer for BAGIM.

Friday, March 1, 2019

BAGIM Event: Yifan Song

Please Join Us on Thursday March 14th at 6pm at Shire on Binney Street for a talk entitled:
Got Structure?
by Yifan Song

Most computational methods that can be applied to drug discovery require a protein structure. Ideally, such structures are derived from experimental approaches such as X-ray, EM or NMR. However, frequently, an experimental structure of the specific protein of interest is not available. In such a case we turn to homology modeling.

The state-of-the-art for homology model prediction has progressed tremendously over the past two decades. Whereas useful HM models were initially only available in cases where a high-similarity homolog was available in the PDB, it is now often possible to predict such models even when the best homologs have only 15-25% similarity to the sequence whose structure is being predicted. The dramatic improvement in what is possible with HM is due to several factors, including: adoption of methods that can identify suitable low similarity templates on the basis of Markov Models, familial and other deep analysis of sequence space; the ability to incorporate multiple low-similarity templates to broadly span a target sequence; powerful approaches to model building that can handle missing structure due to lack of template, insertions and deletions; and the availability of massive compute power through processor clusters and parallelization. In many cases, the HM models that can be generated are so good—not only in terms of backbone trace, but also in such fine details as hydrogen bonding network, salt bridges, disulphide bonds, etc.—that they are suitable for downstream modeling methods.

We will present the history of HM approaches, culminating in a description of the state-of-the-art Rosetta HM workflow.

Friday, January 25, 2019

BAGIM Event: Michael Hoemann

Please join us on Feb 28th at 6pm at Le Meridien for a talk entitled:

Design at AbbVie in the 21 st Century
Michael Hoemann
in collaboration with: Maria Argiriadi, Eric Breinlinger, Kevin Cusack, Jeremy Edmunds and Michael Friedman

This talk will cover the various computational tools that we use at AbbVie at all stages of small molecule drug design. In particular, methods for the analysis of large numbers of virtual compounds through docking (i.e. Glide, Gold etc), clustering (i.e. tSNE), similarity analysis (i.e. Rocs Overlay™ and Cresset Torch™) and sorting through fingerprints (i.e. SIFT) of ligand-protein interactions will be discussed. In addition, it is recognized that protein-ligand complexes are not static solid state structures, but are dynamic and fluid. Therefore, this talk will talk about some of the early work we have been doing at AbbVie to utilize dynamic simulations (MM-GBSA, Desmond MD, MetaDynamics and FEP+) to prioritize compounds for synthesis. These tools when combined together can provide validated workflows to improve the efficiency of small molecule drug discovery.

Tuesday, November 13, 2018

BAGIM Event: Anne Carpenter, Ph.D.

Anne Carpenter will present on "Accelerating drug discovery through the power of microscopy images."

Microscopy images contain tremendous information about the state of cells, tissues, and organisms. We work with biomedical researchers around the world to extract metrics from cell images, particularly in high-throughput screening experiments testing drugs in disease model systems. As the cell systems and phenotypes of interest become more complex, so are the computational approaches needed to properly extract the information of interest; we continue to bridge the gap between biologists’ needs, such as 3D organoid models, and the latest in computational science, such as deep learning algorithms.

Beyond measuring features that biologists specify, we extract even more from images through profiling experiments using the Cell Painting assay, where thousands of morphological features are measured from each cell’s image. We are working to harvest similarities in these “profiles” for identifying how drugs and genes affect cells, identifying the functional impact of cancer-associated alleles, discovering disease-associated phenotypes, and identifying novel therapeutics. Ultimately, we aim to make perturbations in cell morphology as computable as genomics data.

All novel algorithms and approaches from our laboratory are released as open-source software, including CellProfiler, CellProfiler Analyst, and cytominer.

Anne Carpenter is senior director of the Imaging Platform at Broad Institute of MIT and Harvard. Carpenter is now a pioneer in image-based profiling, the extraction of rich, unbiased information from images for drug discovery, and functional genomics. She collaborates with dozens of biomedical research groups around the world to develop and apply image analysis methods to diverse biological questions. Carpenter is an NIH MIRA investigator, an NSF CAREER awardee, and has received recognition and research funding from numerous other groups including the Human Frontiers in Science program and the Howard Hughes Medical Institute. Carpenter earned her B.S. from Purdue University and her Ph.D. from the University of Illinois at Urbana-Champaign.

Please follow her on twitter: @DrAnneCarpenter

Thursday, October 4, 2018

BAGIM Event: Derek Lowe on October 18th at 6pm at Le Meridien

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He’s worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer’s, diabetes, osteoporosis and other diseases. Derek is the author of the widely read "In the Pipeline" blog.


Thursday, September 13, 2018

First BAGIM event of the season: Roy Vaz

Title: A data analysis exercise to decipher kinase antitargets

Roy J. Vaz received his Ph.D. from the University of Florida, Gainesville in Chemistry with Profs. G. B. Butler and M. Zerner. He obtained an undergraduate degree from the Indian Institute of Technology, Bombay. After his Ph.D., he obtained an MBA from the University of Illinois, UC and most recently an MS in Molecular Biology from Lehigh University. He was responsible for managing the CADD, SB and Cheminformatics efforts at Sanofi, Bridgewater, NJ prior to relocating and supporting small molecule discovery at Sanofi-Genzyme, Waltham, MA. He was previously Director of the Investigative Product Optimization department at Aventis in Bridgewater. He has worked with Bristol-Myers Squibb, Hopewell as Principal Scientist as well as Tripos, Inc, St. Louis as a Research Scientist. He has authored or co-authored over 50 publications in peer-reviewed journals, contributed towards many book chapter and several patents and edited 2 books related to Antitargets.

Wednesday, August 8, 2018

Illuminating the Druggable Genome (IDG) Outreach with BAGIM

IDG Outreach meeting with BAGIM
9 am – 2 pm, August 23, 2018
Harvard Medical School
Boston, MA

RSVP Email: idg.rdoc@gmail.com before August 19th, or you will not be able to enter the building.
Come and hear more about Illuminating the Druggable Genome Consortium, a NIH Common Fund program,
composed of Knowledge Management Centers (KMC), Data Resource Generating Centers (DRGC), and
Resource Dissemination and Outreach Center (RDOC).


9:00 Welcome and Introduction - Tudor Oprea, PhD, MD

9:05 Presentation from KMC at University of New Mexico (UNM)
Protein Knowledge Graphs and Machine Learning for
Target Prioritization - Tudor Oprea, PhD, MD

9:30 Presentation from KMC at Icahn School of Medicine at Mt.
Sinai (ISMMS)
Harmonizome-ML: Interactive On-the-Fly Imputation of
Knowledge about Genes and Proteins with Machine
Learning - Avi Ma'ayan, PhD

9:55 Presentation from KMC at National Center for Advancing
Translational Sciences (NCATS)
Pharos, User-Interface to Illuminating Druggable Genome -
Dac-Trung Nguyen and Timothy Sheils

10:20 Break

10:35 Presentation from DRGC - Kinase
Dark Kinase Knowledgebase - Matthew Berginski, PhD
(UNC at Chapel Hill)
Small Molecule Library Informatics - Nienki Moret, Bsc

11:25 Presentation from DRGC - Ion Channel
Data driven co-ablation of Ion Channels - Zicheng Hu, PhD

11:50 Break

12:20 Presentation from outside IDG community
Functional and structural interactions in druggable targets
from evolutionary information - Chris Sander, PhD
Genetic variation in human drug-related genes - Debora
Marks, PhD (Harvard)

13:10 Feedback loop: Discussion on improvements to better
serve the community.

Harvard Medical School
Warren Alpert Building, Room 563
200 Longwood Avenue
Boston, MA 02115

**Attendees**: Please email your name and affiliation to idg.rdoc@gmail.com by August 19, 2018 in order to

pass HMS building security.
BAGIM - Boston Area Group for Informatics and Modeling