Traditional approaches for ligand similarity, such as neighborhood or path based fingerprints, are based on molecular patterns, containing little information about the physics underlying protein-ligand recognition events. I am using a combined cheminformatics and structural bioinformatics approach to construct a thesaurus for ligand-based scaffolds, related via their interaction patterns with proteins from high-resolution x-ray crystals. This thesaurus will then be used to construct 3D interaction fingerprints for use in SEA (Similarity Ensemble Approach), for constraining or filtering virtual screening experiments, and for designing ligand-binding proteins. In developing these interaction fingerprints, we differ philosophically from previous fingerprinting approaches in that we strive to capture statistically enriched many-body interactions instead of painting yet another unsatisfying pairwise landscape.
A Simple Representation of Three-Dimensional Molecular Structure.
J Med Chem. 2017 Sep 14. Axen SD, Huang XP, Caceres EL, Gendelev L, Roth BL, Keiser MJ.
Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds.
Nat Chem Biol. 2016 Jul. Bruni G, Rennekamp AJ, Velenich A, McCarroll M, Gendelev L, Fertsch E, Taylor J, Lakhani P, Lensen D, Evron T, Lorello PJ, Huang XP, Kolczewski S, Carey G, Caldarone BJ, Prinssen E, Roth BL, Keiser MJ, Peterson RT, Kokel D.
Leveraging Large-scale Behavioral Profiling in Zebrafish to Explore Neuroactive Polypharmacology.
ACS Chem Biol. 2016 Apr 15. McCarroll MN, Gendelev L, Keiser MJ, Kokel D.