Understanding Interactions and Recognition in Biological Systems

Principal Investigator: Prof. Alexander TKATCHENKO


Progress in biochemistry and molecular biology is consistently linked to a better knowledge of the structure of, and functional interplay between, biomolecules such as DNA, RNA, and proteins. Even though these building blocks of living matter may appear at first glance to lack a larger systematic order, it is well known that relevant biochemical processes follow precisely timed sequences; in other words, they display a dynamical order. Living cells host chemical reactions catalyzed by enzymes whose critical action accelerates by orders of magnitude the reaction rates of biomolecules via lowering of the free energy barrier. Likewise, DNA/RNA-interacting proteins (e.g., helicases, polymerases, nucleases, recombinases) modulate essential transaction processes involving nucleic acids to achieve DNA duplication and repair, gene expression and recombination, with an astonishing efficiency.

Such an astonishing efficiency raises a fundamental question from a physico-chemical point of view. With biochemical reactions mostly being stereo-specific, reacting partners have to come in close contact and exhibit a definite spatial orientation to initiate particular reactions. Then, how do the various actors in a given biochemical process efficiently find each other (i.e., how does a protein effectively recruit the appropriate co-effector partner(s) or selectively connect with its DNA/RNA target(s) in a crowded cyto/nucleoplasm environment)? In other words, what are the physico-chemical forces that bring all these players together at the right place, in the right order, and in a reasonably short time to sustain cellular function and ultimately cellular life?

The research program in Tkatchenko’s group aims to develop increasingly more accurate quantum-mechanical (QM) methods that can be applied to model interactions in realistic biomolecular systems. We have already demonstrated substantial impact of QM interaction on anisotropic potentials in biomolecular systems and protein folding in water. Ongoing work pushes the applicability of our methods to dynamics of ever more complex biological systems, ultimately aiming to address the questions of recognition and signalling mechanisms in realistic biological models.

Connections to other local activities:

– Esposito: Interactions between biomolecules out of equilibrium

– Skupin: neuronal signalling

Connections to other international activities:

– Institute for Pure and Applied Mathematics: www.ipam.ucla.edu