The interface between biology and physics currently resides at the level of macromolecules and their complexes: Direct application of the canonical laws of physics does not satisfactorily describe much of the general behavior of molecular-level biological systems. Our understanding of topics such as protein folding and function, dynamics of molecular complexes and behavior of systems of interacting molecules can be enhanced through new formalisms of the physical laws of biology. I am interested primarily in using coarse-grained models and statistical physics techniques to elucidate the underlying physical rules that are applied to the elements of living systems. Some particular areas of interest are:

Protein Folding

Proteins are molecules that are responsible for myriad chemical interactions within all living organisms. Each protein acts as a molecular machine that performs a very specific chemical task, and the various proteins within a cell work together in an orchestrated manner to sustain the chemical processes necessary for life. Even though the proteins exhibit remarkable chemical diversity, they are all simply linear chain molecules, the monomers of which are the 20 amino acids coded by the DNA. Under its natural physiological conditions, each protein adopts a distinct native state fold which, along with the chemical properties of the protein's constituent amino acids, endows the protein with the chemical specificity required for proper function. A protein's native state is determined exclusively by its amino acid sequence, but the protein folding problem -- the task of predicting proteins' native states from their amino acid sequences alone -- remains unsolved. My research focuses in part on investigating protein folding and the geometry of protein structures using statistical physics techniques.

Protein Dynamics

As a class of molecules, proteins exhibit the remarkable ability to be simultaneously stable and sensitive. Folded proteins are thermodynamically stable, but many of them -- such as enzymes -- are highly sensitive to specific environmental perturbations. This sensitivity is likely a result of energetic frustration: the physical constraints of the peptide chain force some regions of folded proteins into energetically unfavorable conformations, and the native state has the minimal global energy despite localized high-energy regions. Working under the Structure->Dynamics->Function paradigm, I investigate how local energetic frustration can specifically enhance a the physical sensitivity of proteins.

Supramolecular Dynamics

A great deal of interesting biology occurs between the fine angstrom-scale details of atomic interactions and the micrometer-scale of eukaryotic organelles. Biological activity on the order of hundreds of nanometers is generally neither easily nor accurately modeled using either atomic-level or macroscopic physics. Interestingly, there are several megadalton-scale systems that possess a high degree of symmetry, straddling the line between highly ordered crystalline solids and the fluid organic forms of larger-scale biology. I am interested in investigating the evolutionary, self-organizational and mechanical properties of systems such as the nuclear pore complexes and viral capsids to understand the relevant physics of this unique scale.

Systems Biology and Rational Drug Design

The chemical operation of a cell results from a highly complex network of chemical interactions between genes and their products. When a gene is expressed, its corresponding protein is synthesized and might impact the cell by activating or repressing other genes. New technologies allow researchers to simultaneously probe the levels at which all genes in a cell are expressed, and analysis of this data will uncover the network of interactions that drives life. Part of my researches involves applying principles of statistical mechanics to gene expression data in order to elucidate the network of effective interactions between genes.