Computational Biophysics Group
Computational Biology Branch
   National Center for Biotechnology Information
   National Institutes of Health

In biology we are now at the point where the latest advances of experimental and computational methods have opened a new perspective. Next-generation sequencing technologies allow rapid sequencing of thousands of different genomes, however, these new advances in genome sequencing are necessary but not sufficient for understanding the causes of many diseases. Indeed, specific human phenotype is largely determined by the interactions between numerous biomolecules which work together to provide specific cellular functions. The study of biomolecular interactions is a multidisciplinary endeavor and its ultimate goal is to put pieces of the interaction puzzle together and to characterize complete interactomes - not only all interactions between biomolecules in a given organism, but also the atomic details of these interactions, their binding and regulatory properties.

Along these lines we develop methods which integrate the systems biology approach of looking at complex data from multiple sources with the molecular biophysics approach which zooms down toward a particular specific element of the system and tries to decipher molecular mechanisms. Our methods and approaches aim to: - identify protein interaction partners (proteins, nucleic acids, small molecules) and binding sites on proteins; - perform protein structural modeling and molecular dynamics simulations; - estimate protein binding and folding energy; - predict the effect of disease mutations and covalent modifications on protein stability, binding and activity. One of our goals is to map cellular pathways with as many elements and interactions as possible. From the practical point of view it will provide control and predictive power for the behavior of the system in response to perturbation and disease; it will offer valuable experimental leads for identifying driver mutations and genes in cancer and for designing drugs affecting protein interactions and pathways.


Main current projects
Protein phosphorylation: regulation of binding and activity
Annotation of protein binding sites
Evolution of protein interactions
Effect of disease mutations on protein binding and activity