Tuesday, February 28, 2017

Lecture 15: Prof. Alex MacKerell

From Lemkul, J. A. et. al., Chemical reviews, 2016 [2].
Recent developments in polarizable force field research
Atomistic molecular dynamics (MD) simulations have become an integral component of the tool set used to examine biomolecular systems. Since the first MD simulation of a protein in 1977 [1], the time scales and sizes of computationally tractable simulations have grown by orders of magnitude. Systems may now be simulated on the microsecond or millisecond time scale and contain over a million atoms due to increased computing power and ever-improving algorithms for parallel and graphical processing unit (GPU)-based computing. Such capabilities also allow for more rigorous testing of the accuracy of the models used for such MD simulations.
Molecular mechanics force fields that explicitly account for induced polarization represent the next generation of physical models for molecular dynamics simulations. Several methods exist for modeling induced polarization, and in this seminar, Prof. MacKerell reviewed the classical Drude oscillator model, in which electronic degrees of freedom are modeled by charged particles attached to the nuclei of their core atoms by harmonic springs. He described the latest developments in Drude force field parametrization and application, primarily in the last 15 years. Emphasis was placed on the Drude-2013 polarizable force field for proteins, DNA, lipids, and carbohydrates. He discussed its parametrization protocol, development history, and recent simulations of biologically interesting systems, highlighting specific studies in which induced polarization plays a critical role in reproducing experimental observables and understanding physical behavior. As the Drude oscillator model is computationally tractable and available in a wide range of simulation packages, it is anticipated that use of these more complex physical models will lead to new and important discoveries of the physical forces driving a range of chemical and biological phenomena.
Related References:
[1] McCammon, J. A., Gelin, B. R., & Karplus, M. (1977). Dynamics of folded proteins. Nature, 267(5612), 585.
[2] Lemkul, J. A., Huang, J., Roux, B., & MacKerell Jr, A. D. (2016). An empirical polarizable force field based on the classical drude oscillator model: development history and recent applications. Chemical reviews, 116(9), 4983-5013.
Alex MacKerell received an A.S. in biology in 1979 from Gloucester County College, Sewell, NJ, followed by a B.S. in chemistry in 1981 from the University of Hawaii, Honolulu, HI, and a Ph.D. in biochemistry in 1985 from Rutgers University, New Brunswick, NJ. Subsequent training involved postdoctoral fellowships in the Department of Medical Biophysics, Karolinska Intitutet, Stockholm, Sweden, in the area of experimental and theoretical biophysics and in the Department of Chemistry, Harvard University in theoretical chemistry. Following one year as a visiting professor at Swarthmore College, Swarthmore, PA, he assumed his faculty position in the School of Pharmacy, University of Maryland, Baltimore in 1993. MacKerell is currently the Grollman-Glick Professor of Pharmaceutical Sciences in the School of Pharmacy and the Director of the University of Maryland Computer-Aided Drug Design Center. MacKerell is also cofounder and Chief Scientific Officer of SilcsBio LLC. Research interests include the development of theoretical chemistry methods, with emphasis on empirical force field development; structure–function studies of proteins, carbohydrates, and nucleic acids; and the application of theoretical methods to drug discovery.