Fax number: 212-851-4650
Location: ICRC Room 815 (AUDIII - 1130 St. Nicholas Avenue)
The guiding hypothesis of much of our current research is that sequence and structural information combined with biophysical analysis can reveal how biological specificity is encoded on protein structures. Our efforts in the past few years have focused on the development and application of biophysical and bioinformatics methods aimed at understanding the structural and energetic origins of protein-protein, protein-nucleic acid, and protein-membrane interactions. Our work includes fundamental theoretical research, the development of software tools, and applications to problems of biological importance. In this regard we maintain an active collaborative computational/experimental research program on the molecular basis of cell-cell adhesion. Other problems of current interest include protein structure prediction, the organization of protein sequence/structure space, the prediction of protein function based on protein structure, the structural origins of specificity in protein-DNA interactions, RNA function and, more generally, the electrostatic properties of biological macromolecules.
We use computational and theoretical methods to study the structure and function of proteins, nucleic acids and membranes. A current focus involves the combined use of physical and chemical methods, amino acid sequence analysis, three dimensional structure analysis and data mining as tools in bioinformatics and genome analysis. Specific research areas include: The development of accurate computational methods to predict protein structure from amino acid sequence; the use of three-dimensional structural information to identify relationships between remote sequence homologs and the use of these relationships in the analysis of genomic information; the study of the physical chemical principles that underlie protein and RNA folding, protein-protein, protein-nucleic acid and protein-membrane interactions; the development of computational methods to identify protein function based on protein structure; the application of computational tools to the understanding of problems of biological importance such as subcellular localization in protein/membrane systems and the specificity of protein-protein interactions in signaling pathways.
As part of our research program we make a significant effort in software development. The programs we have developed include: DelPhi, which calculates the electrostatic properties of biological macromolecules; GRASP, which maps electrostatic and other properties on macromolecular surfaces; GRASS, which is a web-based GRASP server; SPIN; a server to describe interfaces formed by Macromolecules; PrISM (Protein Informatics System for Modeling). PrISM is an interactive program that analyzes protein sequences and structures and contains novel threading and homology modeling techniques.
Chen, C. P., Posy, S., Ben-Shaul, A., Shapiro, L. and Honig, B. (2005) Specificity of Cell-Cell Adhesion by Classical Cadherins: Critical Role for Low-Affinity Dimerization Through β-strand Swapping. Proc. Natl. Acad. Sci. USA 102:8531-8536.
Petrey, D. and Honig, B. (2005) Protein Structure Prediction: Inroads to Biology. Mol. Cell. 20:811-819.
Joshi, R., Passner, J.M., Rohs, R., Jain, R., Sosinsky, A., Crickmore, M.A., Jacob, V., Aggarwal, A.K., Honig, B. and Mann, R.S. (2007) Functional Specificity of a Hox Protein Mediated by the Recognition of Minor Groove Structure. Cell 131:530-543.
Posy, S., Shapiro, L. and Honig, B. (2008) Sequence and structure determinants of strand swapping in cadherin domains: Do all cadherins bind through the same adhesive interface? J. Mol. Biol. 378:952-966.
Forrest, L.R., Zhang, Y.-W., Jacobs, M.T., Gesmonde, J., Xie, L., Honig, B. and Rudnick, G. (2008) A Mechanism for Alternating Access in Neurotransmitter Transporters. Proc. Natl. Acad. of Sci. 105:10338-10343.