Stefano Monti, Core Leader
Boston University School of Medicine, Department of Medicine
Sandor Vajda, Co-Leader
Boston University, Department of Biomedical Engineering
The Bioinformatics and Molecular Modeling Research Support Core (BMMC) offers computational tools, expertise, and services to BUSRP projects (Project 3, 4, and 5, and interactions), in three areas: (1) analysis of data obtained by high throughput genomic technologies (microarray experiments and RNA-sequencing]), including reconstruction and visualization of regulatory pathways, and integration with data from public repositories; (2) development and application of a high-throughput expression profiling platform and associated computational models for the screening of chemical perturbations in vitro, which will allow the Projects’ investigators to analyze the transcriptional response to xenobiotics of interest, as well as the role played in it by the protein receptors and regulators under study, in multiple cellular contexts (cell lines); and (3) modeling interactions between xenobiotics and protein receptors and cytochrome P450s, using structural bioinformatics and computational biology, including tools originally developed for structure-based drug design, and further modified by the BMMC.
FTMap (http://ftmap.bu.edu): FTMap is a computational mapping server that identifies binding hot spots of macromolecules, i.e., regions of the surface with major contributions to the ligand binding free energy. To use FTMap, users submit a protein, DNA, or RNA structure in PDB format. FTMap samples billions of positions of small organic molecules used as probes and scores the probe poses using a detailed energy expression. Regions that bind clusters of multiple probe types identify the binding hot spots, in good agreement with experimental data.
FTSite (http://ftsite.bu.edu): The goal of FTSite is the identification of ligand binding sites based on the structure of ligand-free proteins. The method is based on the observation that the binding site of a macromolecule generally includes a strong “main” hot spot and some other hot spots that are close enough to be reached by a ligand binding at the main hot spot. The program uses the consensus sites (CSs) detected via the FTMap server to identify and rank binding sites.
FTFlex (http://ftflex.bu.edu): FTFlex performs repeated mapping calculations while exploring low energy conformers of side chains in the vicinity of user-selected hot spots29. The primary goals of this approach are opening pockets in protein-protein interfaces that are potentially capable of binding small molecular inhibitors, and to determine the druggability of such sites.
FTMap/param (http://ftmap.bu.edu/param/) FTMap/param enables the user to define small molecules that are not included in the standard FTMap probe set, to use the mapping program to generate low energy clusters of these additional molecules, and to check the locations of these clusters relative to the hot spots based on the original probes.
- OCT 2017 The Carcinogenome Project launched
- OCT 2017 BUSRP leaders participate in Find the Cause fundraiser
- JUN 2017 BUSRP program-wide meeting strengthens collaborations
- MAY 2017 Stefano Monti gives keynote at BD2K-LINCS Data Science Symposium
- MAY 2017 BUSRP supports Art beCAUSE fundraiser for environmental science
- APR 2017 BUSRP co-hosts Northeast Superfund Research Program Meeting
- MAR 2017 Stephanie Kim presents on Health Sciences Poster Winners webinar
- MAR 2017 Director Sherr presents on computational model developed by BMMC
- JAN 2017 Trainee Stephanie Kim presents at EH seminar
- DEC 2016 BUSRP presents at NIEHS FEST
- SEP 2016 BUSRP presents at NIH LINCS meeting
- JUN 2016 David Sherr interviewed on breast cancer consortium
- OCT 2015 BUSRP to co-host mini symposium
- SEP 2015 BUSRP receives supplement to develop genomic analysis platform
- DEC 2014 Collaborative SRP publication featured in EHP’s Science Selection
- NOV 2014 Trainees Attend 2014 SRP Annual Meeting
- SEP 2014 NIEHS Environmental Factor Features Bioinformatics Core
- JUL 2014 Genomic Models of Exposure Predict Chemical Carcinogenicity
- JAN 2014 Computational Biomedicine Seminar Series features SRP trainees
- DEC 2013 Training & Outreach Day at the Museum of Science, Boston
- OCT 2013 ARC Mini-Symposium: Computational Genomic Models of Environmental & Chemical Carcinogenicity
- OCT 2013 Daniel Gusenleitner wins 1st Place Biomedical Student Poster Competition
- SEP 2013 Dr. Stefano Monti invited attendee of NIEHS/NTP’s effort to nominate and prioritize environmentally responsive genes
- AUG 2013 Collaborative work receives SRP supplement award
- JUN 2013 Offshoot of BUSRP research identifies AhR’s role in blood cell development
- JAN 2013 Mini-symposium on Computational Genomic Models of Environmental and Chemical Carcinogenicity
- OCT 2012 BUSRP Co-hosting Upcoming Symposium
- APR 2009 New publication from the Bioinformatics Core