About Boltzmann Maps Our mission is to fuel medicinal chemists' creativity to more rapidly design novel pharmaceutical compounds that achieve pre-clinical milestones, using significantly fewer resources.
We do that by delivering to the chemistry designer important information and new ideas about drug compounds from modeling, public databases, literature, and other Web services. This information is provided in an easily-to-use, highly-integrated fashion, readily accessible everywhere via the World Wide Web.
A particular emphasis is on fragment-based design methodologies, where maps of how small chemical fragments bind to proteins are interrogated to find ideas for substitutions, extensions, or deletions of chemical groups. These modifications improve the affinity, ligand efficiency, and other properties of lead compounds. Our goal is to make available 1,000's of fragment maps on 1,000's of therapeutically-relevant macromolecules (protein, DNA, RNA).
When a chemist has some active starting compounds (say, from an experimental fragment screen), they often want to obtain information on options for improving the pharmacological performance of these compounds. This includes potency (binding affinity) or the impact on binding affinity of changes envisioned by the chemist to improve ADME properties. Such information helps prioritize which compounds to pursue further.
In pursuit of that goal, a chemist benefits from visualizing the components of interactions between a compound and the target protein to obtain guidance on what to change about the compound to improve binding or avoid making binding worse. These components include the familiar hydrogen bonds, and less readily available, but important elements, such as desolvation costs, bond stresses, bound water interactions, and changes in conformational entropy.
A chemist can be aided by suggestions for chemical modifications to a compound under consideration, that will add additional interactions, fill near-by pockets, displace or link to bound waters, etc.
One-click access to reaction databases and literature about their modified compound will considerably expedite the chemist's design work.
A chemist wants tools to be extremely easy to use and access, because the tools may only be used periodically during the course of projects. The tools must be affordable by small groups.
A chemist wants information provided by tools to be reliable, something they can depend upon.
Our team has hundreds of man-years of experience in producing and applying fragment maps in drug discovery campaigns at Stanford Research International (previously Sarnoff Corp.), Locus Pharmaceuticals, BioLeap, and now Conifer Point.
This Web site builds upon 3DMol for molecular visualization:
Nicholas Rego and David Koes, "3Dmol.js: molecular visualization with WebGL", Bioinformatics (2015) 31 (8):
1322-1324 doi:10.1093/bioinformatics/btu829. 3dmol.csb.pitt.edu
This Web site uses LS-align for ligand alignment:
Jun Hu, Zi Liu, Dongjun Yu, Yang Zhang LS-align: an atom-level, flexible ligand structural alignment algorithm for high-throughput virtual screening. Bioinformatics, in press (2018). zhanglab.ccmb.med.umich.edu/LS-align
This Web site uses SmilesDrawer for 2D visualization:
Daniel Probst and Jean-Louis Reymond, "SmilesDrawer: Parsing and Drawing SMILES-Encoded Molecular
Structures Using Client-Side JavaScript", Journal of Chemical Information and Modeling (2018) 58 (1), 1-7
doi:10.1021/acs.jcim.7b00425. reymond-group/smilesDrawer
This Web site incorporates Open Babel for file format conversion:
Noel M O'Boyle, Michael Banck, Craig A James, Chris Morley, Tim Vandermeersch and Geoffrey R Hutchison,
"Open Babel: An open chemical toolbox", Journal of Cheminformatics (2011) (3) 33:
doi.org/10.1186/1758-2946-3-33 openbabel.org
The development of the Boltzmann Maps Web site was supported by National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health under award number R43GM109549.