Research Interests

Non-covalent Interactions in Chemistry, Biology, and Materials Science

Non-covalent interactions are fundamental toward molecular function. A subtle interplay between specific (hydrogen bonding, halogen bonding) and non-specific (electrostatic, dispersive) interactions govern complex molecular processes like catalysis, molecular recognition, protein folding and misfolding, supramolecular chemistry, crystal engineering, etc. It is extremely challenging to decipher and quantify these interactions even in smaller molecular units let alone bigger macromolecules like protein. Using vibrational Stark Spectroscopy, we access the non-covalent interactions experimentally in a quantitative fashion. Starting from small model conmpounds (which act as building blocks in macromolecules) to larger proteins and macromolecules, we study the role of these interactions toward stability, activity and function. Further, theoretical calculations are performed to compare our experimental results and to obtain a molecular level understanding about the origin of each of these interactions. Additionally, our experimental results provide an opportunity to evaluate the accuracy of the widely used molecular dynamics force fields in recaitulating experimentally observed spectra. We are currently pursueing projects to quantify the contribution of electrostatics and hydrogen bonds to catalytic rate enhancement in organic and biological reactions.

Structural and Conformational Dynamics in Chemistry, Biology, and Materials Science

 Molecular functions are intimately related to their ability to undergo structural and conformational changes. Transient interactions, when coupled to dynamics, add further layers of complexitites to the structure-function relation. It is extremely challenging to experimentally access the ultrafast motions of macromolecules happening in sub-picosecond timescale, however, simulations have predicted the importance of these motions toward funtion (chemical/biologiccal reaction happening at a slower timescale). Using 2D-IR spectroscopy and other time resolved ultrafast spectroscopic techniques, we study the timescales of the ultrafast structural fluctuations and conformational dynamics. The timescales of bond vibrations incorporate the time ranges of these fluctuations, thus, correlating the frequencies along the time trajectories using time resolved IR measurement can quantify the ultrafast structural dynamics. The specific research problems involve structural dynamics in enzyme active site, residue specific conformational changes in ion-channels, ultrafast fluctuations in the cavities of host-guest complexes, real time aggregation pathways of misfolded proteins.