   Department: Theoretical Studies Institution: Institute for Molecular Science, National Institutes of Natural Sciences Lab: Hirata Lab Phone: +81 564-55-7257 Room: 309 Email: sindhikara(AT)gmail.com Address: Institute for Molecular Science, National Institutes of Natural Sciences, 38 Nishigo-naka, Myodaiji, Okazaki 444-8585, Japan  “…it all works because Avogadro’s number is closer to infinity than to 10.” R. Baierlein, Am. J. Phys., Vol 46, No. 10, October 1978.  I study and create analytical tools for computational study of biological molecules. Primarily I work in the classical/atomistic regime making use of statistical mechanical techniques such as liquid state theory and generalized ensemble theory to ascertain biologically relevant information with both accuracy and efficiency.  I am currently employed as a postdoctoral research associate with Professor Fumio Hirata at the Institute for Molecular Science in Okazaki, Japan. My research experience includes a variety of molecular simulation techniques, which I learned and applied in many institutions both in the United States and Japan: University of Florida; University of California, Los Angeles; Nagoya University; and the Institute for Molecular Science (part of the Japan's National Institutes for Natural Science). I received my PhD from the Department of Physics at the University of Florida (UF) under Professor Adrian Roitberg. With him I investigated optimization of replica exchange method (REMD). REMD is an enhanced sampling technique designed to speed up sampling of molecular dynamics simulations. Our work on this project resulted in two publications; including one where an undergraduate student whom I mentored contributed major work. With that student, Daniel Emerson (now in graduate school at University of Pennsylvania), I continue to do work on analyzing convergence of parallel sampling techniques. Professor Roitberg and I also collaborated with Dr. Arthur Voter at Los Alamos National Laboratory on a project investigating potential pitfalls of accidental misuse of molecular dynamics thermostats. Also at University of Florida, I worked with Professor Kenneth M. Merz Jr. along with Professor Roitberg using molecular dynamics to analyze allosteric function of NikR, a metal regulatory protein. That project required the difficult task of parameterizing a metal coordination site, as well as novel fluctuational analysis. After graduating, I spent 1.5 months as a guest researcher at Professor Kendall Houk’s lab at UCLA where I performed QM/MM umbrella sampling simulations to analyze the catalytic potential of designed enzymes. The simulations involved comparative analysis of the reaction path landscape between a water-solvated and an enzyme-catalyzed substrate. The results not only confirmed the success of the designed enzyme, but also illustrated key interactions otherwise undetectable. I then moved on to a postdoc position at Professor Yuko Okamoto’s lab at Nagoya University, Japan where I had spent 2 months previously as a graduate student for a summer fellowship. With Professor Okamoto, I learned advanced enhanced sampling techniques including multicanonical replica exchange method, and implemented that into the AMBER molecular simulation suite. As a postdoctoral researcher, I developed a novel enhanced sampling method, “Frypan Sampling”, which enhances reaction coordinate exploration.I began new work with Professor Fumio Hirata at the Institute for Molecular Science in Japan where I am studying molecular recognition via the statistical theory of liquids known as RISM theory. Here, I have completed a study locating buried solvent molecules inside photoactive yellow protein, and am currently performing studies applying this method to drug design for neuraminidase inhibitors. In summary of my work, I have worked on developing, implementing, and applying a vast array of techniques for molecular simulation. I studied these various techniques in collaboration with many professors at multiple institutions both in the United States and Japan. Please see my CV or publication list for more detail. Research keywords: enhanced sampling, molecular dynamics, Monte Carlo, replica exchange molecular dynamics, QMMM, NikR, Langevin dynamics, AMBER, synchronization, convergence, ergodicity, metalloproteins, metal modeling, WHAM, Frypan sampling, RISM theory, molecular recognition, fragment-based design, drug design, neuraminidase  |
