Alexey Onufriev

The Simple Approaches to Complex Biology

In this presentation I will argue that it is the very simple theoretical/computational approaches that may be robust enough to provide insights into complex phenomena that involve bio-macromolecules. I will exemplify the point with two recent research projects in my group:

1) How is the nucleosome stability modulated?

The primary level of DNA compaction in living cells is the nucleosome.  Modulation of the nucleosome's stability is one of the key aspects of chromatin regulation, which in turn is vital for the fundamental cellular processes such as DNA replication, repair, transcription, and epigenetic inheritance. Yet, exactly how this modulation is accomplished in Nature remains unclear.  I will demonstrate how a model based on basic electrostatics may provide an answer -- alteration of the nucleosome core charge. The latest results of a comprehensive study of all possible charge-altering post-translational modifications (acetylations and phosphorylations) in the nucleosomal core will be presented.

2) Computational identification of pathways of ligand migration in myoglobin.

Exactly how do small non-polar molecules such as O2 or CO travel from the outside of the protein to the deeply buried binding site in myoglobin? I will show how this 50 year old puzzle in molecular biophysics can be addressed by conceptually simple computational means.

Alexey Onufriev is Associate Professor of Computer Science and Physics at Virginia Tech.  For more information please visit:http://people.cs.vt.edu/~onufriev/