Research in my laboratory incorporates large-scale computer simulations with classical physics, chemistry and biology. Current developments include expanding programs to treat large biological molecules (e.g., DNA and F-actin) and exploring quantum mechanical methods for treating small biological molecules such as short peptides. Specific projects in the group include: (1) glycolytic enzyme interactions with cytoskeletal structures; (2) genome regulatory proteins interacting with DNA, and (3) calculating the circular dichroic spectra of small peptides.

(1) The cytoskeletal structure, F-actin creates a structure in the cell cytoplasm upon which glycolytic enzymes associate and dissociate dynamically, and these dynamic associations are important to organizing the reactions in the glycolytic pathway. Many glycolytic enzymes including fructose-1,6-bisphophsate aldolase (aldolase), glycerladehyde-3-phosphate dehydrogenase (GAPDH), and lactate dehydrogenase (LDH) bind actin reversibly. Other enzymes such as triose phosphate isomerase (TIM) bind indirectly through interactions with the enzymes that bind. We use and enhance existing theoretical methods to better investigate the interactions of F-actin with glycolytic enzymes. The method of Brownian dynamics (BD) predicts the various kinds of complexes between F-actin and the glycolytic enzymes, provides the relative stability of complexes, reproduces experimentally observed factors on binding such as ionic strength, pH, and relative binding affinities, and make predictions about the impact of mutations on the proteins.