Understanding Protein-RNA Recognition Using Alchemical Free Energy Calculations 

Dr. Amit Kumar 

Department of Physics and Astronomy 

Wayne State University  

Time: Tuesday, February 28 at 3:30 pm 

Location: 245 Physics Building  

                                                                                       Abstract 

 Alchemical free energy calculations are increasingly being applied in academic research and the pharmaceutical industry. These methods originate in theories of Kirkwood and Zwanzig, where Kirkwood introduced a coupling parameter approach, and Zwanzig showed that the free energy difference between two states can be computed via an appropriate exponential average of energy differences over an ensemble of configurations. In recent years, alchemical free energy calculations have benefited from improved force fields, new sampling algorithms, and the emergence of parallel computing, which have been shown to yield accurate results. These calculations are routinely applied to large-scale free energy calculations for ligand modification, and for testing mutations in amino acids and nucleotides. Modifications introduced in RNA-Protein/peptide complexes using alchemical calculations (i.e., free energy perturbation (FEP) and thermodynamic integration (TI) methods) suggest that the proteins/peptides employ base-specific hydrogen bonding, sugar-phosphate backbone interactions, and cation-pi interactions for the recognition of RNA molecules.  

Bio: Dr. Kumar is a Postdoctoral Researcher in the department of Physics and Astronomy at Wayne State University (WSU). Before joining WSU, I worked as a postdoctoral research associate at the University of New Hampshire and as a senior project engineer at the Indian institute of technology, India. I obtained my Ph.D in computational biophysics from the Indian institute of technology, Guwahati. My research focuses on applying molecular dynamics simulations and alchemical free energy calculations to understand the recognition mechanisms of RNA-Protein/Peptide complexes.