Theoretical and Computational
Biophysical Chemistry Lab​
Research Statement
At the heart of our research lies a fascination with unraveling the mysteries of molecular interactions and their profound implications on larger-scale phenomena. Blending the realms of Chemistry, Physics, Biology, and Materials Science, we embark on a journey of discovery where statistical mechanics and computational modeling serve as our guiding principles. Our multidisciplinary approach converges on three captivating domains: Protein Biophysics, delving deep into the enigmatic world of Protein Aggregation; Nucleic Acid Biology, where our focus illuminates chromatin dynamics and the conformational dynamics of non-canonical nucleic acid structures; and the Chemical Physics of Polymers, where we explore novel avenues for drug delivery and medicinal applications. In our investigations, we explore new frontiers, providing not only valuable insights but also potential solutions that could significantly impact the future of both science and medicine.
​
Here are some research problems that we have been actively working on:
Chromatin Dynamics
Our group in this problem aims to uncover the dynamics of chromatin, the packaging unit of genes that contains all the information in living organisms. Using both conventional and advanced simulation techniques, such as umbrella sampling and metadynamics, we study the dynamics of the nucleosome—the basic building block of chromatin. The nucleosome is formed by wrapping of ~147 nucleotide base pairs around an octameric histone protein, comprised of H2A, H2B, H3, and H4 dimers. One primary objective of our work is to establish the relationship between sequence and nucleosome dynamics, particularly the motions facilitating DNA unwrapping from the histone core. Additionally, we are investigating the effect of histone post-translational modifications on the DNA wrapping/unwrapping dynamics of nucleosomes.
Intrinsically Disordered Protein: Aggregation, Amyloidosis
Our research group focuses on untangling the complex behavior of intrinsically disordered proteins (IDPs), which, unlike globular proteins, do not have a native three-dimensional conformation but exist as an ensemble of conformations. We primarily study IDPs whose aggregation into amyloid leads to devastating neurodegenerative diseases like Alzheimer’s and Parkinson’s. Our primary objective is to reveal the microscopic mechanisms driving aggregation, identify critical intermediates along this pathway, and propose innovative therapeutic strategies to advance drug development. In addition, we are exploring exciting possibilities such as local heating, magnetic/electric fields, and molecular crowding to disintegrate stubborn amyloids and inhibit the overall aggregation process.
Protein Structure and Dynamics
One of our research interest focuses on understanding the classic yet puzzling structure-function relationship of proteins. We primarily investigate the folding pathways of proteins and characterize unfolded intermediates, aiming to provide experimentalists with strategies for structure-aided drug design. Currently, our main focus is on metamorphic proteins, which have multiple functionally important native states. We use and often develop advanced simulation techniques to address this problem, frequently validating our predictions with single-molecule experiments.
Hydration and Protein Behavior
One key research interest of our group is understanding the role of hydration water in protein activity through computer simulations. We focus on the relationship between hydration water behavior and protein functionality, characterizing the structure and dynamics of hydration water to correlate with protein folding and unfolding. We also microscopically track specific waters confined within protein domains, such as active sites, to determine their role in controlling protein folding and aggregation, which can lead to amyloids associated with neurodegenerative diseases. Our computational studies aim to uncover the critical influence of hydration water on these biological events.
