Where would we be without drugs? Pharmaceuticals cure disease and enable modern life as we know it. Yet, in spite of how far we have come, there is still much more work to do. Cancers and infectious diseases are constantly evolving resistance to existing medicines. Furthermore, there are many diseases, especially those which primarily affect the developing world, which have no satisfactory treatment.

A major obstacle to drug development is its large expense. It has been estimated that the cost of bringing a drug to market ranges from $800 million to over one billion. A long term goal of my research is to find more cost-effective means of drug discovery. While there are many good ways to go about this, I like to focus on molecular biophysics and statistical mechanics.

Molecular Biophysics

Molecular biophysics is the study of the physical properties of biological molecules. It is relevant to drug discovery because most pharmaceuticals work by physically binding to enzymes and stopping them from working. I have worked on and used a variety of methods to try to better understand molecular biophysics.

These include

• Molecular dynamics computer simulations - After constructing a 3D virtual model of a molecular system (such as a protein in water), the motions of the model are simulated. These simulations have been used, for example, to look for possible drug binding sites in avian flu.
• Solution wide-angle x-ray scattering (WAXS) - While biomolecules are usually studied in a dilute or crystalline environment, physiological conditions are quite different. X-ray scattering can be used to probe the structure of biomolecules in solutions and observe the extent to which they breathe.
• Single-molecule force spectroscopy - it is now possible to mechanically stretch single biomolecules and measure the force that these molecules exert at different extensions. I have worked on methods for interpreting these experiments.

It is one thing to do an experiment, and another to understand what it means. Statistical mechanics is the science of obtaining macroscopic thermodynamic information from microscopic information. It is particularly relevant to the effective design and analysis of molecular dynamics simulations and single-molecule force spectroscopy experiments.

I have been especially active in nonequilibrium statistical mechanics, in which information about systems in equilibrium is obtained from experiments of the system out of equilibrium. In addition to continuing this work, I'd like to develop methods to more efficiently calculate free energies (such as how well a drug sticks to a protein).