Research Interests
We use multiscale computational modeling to investigate complex biological systems spanning bacteria, viruses, and light-sensitive proteins with a particular emphasis on the native protein, lipid, and sugar environments.
Long-range charge transport
Utilization of multi-heme cytochromes (MHCs) in the “respiration” of anaerobic bacteria makes them attractive candidates for emerging biotechnological applications like bioremediation of contaminated soil, microbe-to-electrode and electrode-to-microbe charge transport (CT) in microbial fuel cells and biofuel production. Therefore, the ability to control the rate of CT to/from redox-active toxins and electrodes will be instrumental for these technologies.
The outer membrane (OM) of Gram-negative anaerobic bacteria modulates the CT rates influencing their respiration. We aim to understand the mechanism of “respiration” machinery in anaerobic marine bacteria with an emphasis on the role of the OM.
Excited-state force field
Excited-state processes are ubiquitous in nature and biotechnology. Photoinduced conformational changes that occur well beyond a few nanoseconds are still inaccessible to modern multiscale quantum mechanics/molecular mechanics (QM/MM) techniques. While molecular dynamics can access timescales of hundreds of microseconds with enhanced sampling techniques, it can only represent the ground state of a molecule due to limitations imposed by force-field parameters.
We design excited-state force field parameters for specific states of biologically relevant molecules. These parameters enable longer sampling of a "frozen" excited state.
Excited-state allostery
Nature uses photosensing to regulate cellular processes. A molecule absorbs light and initiates a series of downstream events to achieve the desired outcome. For example, blue light-sensitive proteins, namely, light-oxygen-voltage-sensing (LOV) and sensors of blue-light using FAD (BLUF), control processes like enzymatic activities, transcription, metabolism, signaling by a second messenger, and establishing the membrane potential.
Light-induced events in BLUF proteins involve subtle changes in the hydrogen bonding network around the bound flavin cofactor that transmit an allosteric signal over a distance, ultimately inducing a specific activity as output. To this end, we investigate the pathways of signal transmission from the flavin cofactor to the output site.
Coronavirus spike protein
Betacoronaviruses have created three separate epidemics in the last twenty years, namely, SARS, MERS, and COVID-19 forewarning their relevance in the future. The glycans on the spike protein of each of these coronaviruses shield the viral spike protein, which binds to human receptors, from immune detection. Some glycans may assist the spike protein opening required for the receptor binding. Therefore, they reduce potential vaccine efficacy and make the virus more infectious. The exact nature and chemical composition of glycans are inaccessible to imaging techniques.
We characterize the viral and receptor glycans in multiple betacoronaviruses using modeling studies and molecular dynamics as the “computational microscope”.