(735ab) Molecular Simulation Methods to Probe Dynamics and Thermodynamics in Nucleoprotein Systems

Research interests: The focus of my past research has been the computational modeling and characterization of various biomolecular systems, including nucleic acids, proteins, and membrane systems. As part of my future work, I am interested in expanding my research work on RNA molecules by characterizing the energetic and structural effects of chemical modifications in DNA molecules by performing alchemical free energy calculations of these modifications. Results from these simulations will be useful in the design and functionalization of DNA nanostructures which can be further used in the drug delivery process. Furthermore, I am interested in applying computational modeling in understanding how the host-cell DNA strands are properly positioned prior to integration of the viral DNA genome in the viral intasome complex as well as the subsequent conformational changes which the intasome undergoes during the multistep integration process of the viral genome into the host-cell genome. Insights from these simulations will be useful in designing novel integrase strand transfer inhibitors (INSTIs). As my last project, I would like to develop coarse grained models of DNA molecules to characterize DNA packaging into chromatin fibers which is an essential biophysical process in cells.

PhD Dissertation: Molecular Simulation Studies of Dynamics and Interactions in Nucleic Acids. Advisor: Harish Vashisth at University of New Hampshire.

Postdoctoral Projects: Characterization of the Molecular Architecture of the HIV or Related Viruses. Under the supervision of Prof. Juan R. Perilla.

Studying Transmembrane Protein Dimerization Using Coarse Grained Simulations. Under the supervision of Prof. Harish Vashisth.

Successful Proposals: Juan R. Perilla Postdoctoral Researcher. Assisted in writing and gathering preliminary data for ACCESS and DARWIN supercomputing facilities.

Additional Proposal Writing Experience: Harish Vashisth Postdoctoral Researcher. Assisted in writing and gathering preliminary data for the NSF MFB project.

Teaching interests: During my doctoral and postdoctoral assignments, I had the opportunity of training several undergraduate and graduate students in developing skills and knowledge necessary to conduct molecular simulations. As a TA, I had the opportunity to teach both core chemical engineering courses such as unit operations and transport phenomena as well as an elective course to students with diverse backgrounds. As a chemical engineering faculty, I am ready to teach any core chemical engineering course or any other elective that fits my professional background. As an example of an elective course, I would like to introduce students to the fundamentals of bioengineering/biophysics while further emphasizing how molecular modeling, simulation, and visualization techniques can assist us in understanding biomolecular structures.

Research experience: During my doctoral research I focused on studying dynamics and interactions in viral nucleic acids. Specifically, I have worked on the HIV-1 RNA molecules and their interactions with ligands of various sizes, ranging between small inhibitory molecules and peptides with inhibitory properties. Furthermore, I have utilized a toolkit of enhanced sampling and path sampling techniques to characterize several essential biophysical processes in nucleic acids: ligand (un)binding and base flipping mechanism. These projects provide additional understanding of how local and global conformational transitions in RNA facilitate interactions of RNA with a diverse set of ligand molecules. My postdoctoral experience has further expanded the scope of systems and methodology which I am proficient in. Specifically, I worked on the retroviral replication process with the focus on studying how clinically-approved drugs perturb essential steps in the replication cycle of HIV-1. During that period, I collaborated with experimental groups to refine experimentally resolved structures and fill in the gaps that are missing from experimental data. I also gained experience in writing first-authored manuscripts, co-authored manuscripts while providing guidance to a PhD student, as well as working in large collaborative projects exchanging data with researchers from across and outside the country.

Selected Publications:

Levintov, L., Paul, S., and Vashisth, H. (2021) “Reaction coordinate and thermodynamics of base flipping in RNA.” J. Chem. Theory Comput., 17 (3), 1914-1921.

Singer, M. R., Dinh, T., Levintov, L., Annamalai, A. S., Rey, J. S., Briganti, L., Cook, N. J., Pye, V. E., Taylor, I. A., Kim, K., Engelman, A. N., Kim, B., Perilla, J. R., Kvaratskhelia, M., and Cherepanov, P. (2023). “The mechanism of HIV-1 integrase aggregation by allosteric inhibitors.” mBio., 14 (1), e03560-22.

Krebs, A. S., Liu, H. F., Zhou, Y., Lancheros, J. S. R, Levintov, L., Shen, J., Howe, A., Perilla, J. R., Bartesaghi, A., Zhang, P. (2023). “Molecular architecture and conservation of an immature human endogenous retrovirus.” Nat. Commun., 14 (1), 5149.

Levintov, L., and Vashisth, H. (2024). “Structural and Computational Studies of HIV-1 RNA.” RNA Biol., 21 (1), 1-32.

Levintov, L., and Vashisth, H. (2024). “Adenine Methylation Enhances the Conformational Flexibility of an RNA Hairpin Tetraloop.” J. Phys. Chem. B, 128 (13), 3157–3166.