The Use of Quantitative Sciences to
Understand Complex Biological Processes
Professor Jose Onuchic
University of California at San Diego
Department of Physics, 7226 Urey Hall
La Jolla, CA 92093-0319
(619) 534-7067
Biology is going through a golden period during which it is being transformed from a qualitative to a quantitative science. Several scientists coming from chemistry and physics, and to some extent computer science and applied mathematics, have been making use of their quantitative techniques and theoretical framework to provide substantial contributions to biology. It is becoming more and more apparent to the scientific community that physical approaches are helpful towards a quantitative understanding of biological phenomena. I could describe several different problems where such a transformation is apparent, but I will limit my examples the two different main efforts in my research group: protein folding and electron transfer in proteins. The short description that follows for these two problems provides examples of how physical approaches can be used for a quantitative understanding of these complex problems.
Inspired by ideas from chemical physics and modern statistical physics (particularly for disordered systems), a new viewpoint for protein folding has been developed. Energy landscape theory and the funnel concept provide the theoretical framework, asserting that a full understanding of the folding process requires a global overview of the landscape. The folding landscape of a protein resembles a partially rough funnel riddled with traps where the protein can transiently reside. Convergent kinetic pathways, or folding funnels, guide folding to a unique, stable native conformation. Connections between our theoretical advances and experiments are central for the development of this new view for protein folding. I believe that this is a great example of a problem for the Institute for Complex Adaptive Matter.
A second topic I want to discuss is the theory of chemical reactions in condensed matter with emphasis on biological electron transfer reactions. These reactions are central to the bioenergetic pathways of both animals and plants on earth, such as the early steps of photosynthesis. We have investigated several aspects of this problem: the role of quantum dissipation and coherence, adiabaticity and non-adiabaticity of reaction rates, energy redistribution, the validity of the Born-Oppenheimer approximation and two-level system Hamiltonians in biochemical reactions. Most of our recent work deals with the electronic coupling between the donor and acceptor sites. The concept of tunneling pathways and the methodology for reducing the protein into a combination of relevant tubes of pathways create a new way of designing electron transfer proteins. The connection between this theoretical approach and experiments in electron transfer proteins has substantially improved our understanding of these electron transfer processes. This problem provides a clear example of how sophisticated theoretical techniques have been used to understand important biological processes and to design novel systems that mimic biology.