Advanced Sampling for Biomolecular Simulations

Biological molecules exhibit complex dynamics on timescales varying from subnano to milliseconds and beyond, due to free energy barriers of different heights. Traditional MD simulations have difficulty on studying these complicated behaviors on timescales longer than milliseconds even using large-scale high performance computing resources or highly specified expensive computer chips. Advanced sampling algorithms are the alternative methods. To overcome this timescale challenge on protein-ligand binding and slow conformational dynamics, some of my major work at Temple University included developing large-scale multidimensional asynchronous replica exchange (AsyncER) algorithm, combining AsyncRE with biasing potentials for rescaling inter and intra-interactions of ligand/receptor, and improve corresponding reweighting techniques for massive simulations. In addition to REMD methods for binding free energy calculations, I also used various advanced sampling methods such as map-restrained langevin dynamics, Markov state modeling, metadynamics and adaptively biased molecular dynamics for exploring free energy landscapes of conformational changes.

Asynchronous Replica Exchange MD Stochastic Solution of UWHAM Equations
  1. Junchao Xia, William Flynn, and Ronald Levy, " Improving prediction accuracy of binding free energies and poses of HIV integrase complexes using the binding energy distribution analysis method with flattening potentials," J. Chem. Info. Model. 58, 1356 (2018).
  2. Junchao Xia, William F. Flynn, Emilio Gallicchio, Bin W. Zhang, Peng He, Zhiqiang Tan, and Ronald M. Levy, " Large scale asynchronous and distributed multi-dimensional replica exchange molecular simulations and efficiency analysis," J. Comput. Chem. 36, 1772 (2015).
  3. Emilio Gallicchio, Junchao Xia, William F. Flynn, Baofeng Zhang, Sade Samlalsingh, Ahmet Mentes, and Ronald M. Levy, " Asynchronous replica exchange software for grid and heterogeneous computing," Comput. Phys. Comm. 196, 236 (2015).
  4. Bin W. Zhang, Junchao Xia, Zhiqiang Tan, and Ronald M. Levy, " A stochastic solution to the unbinned WHAM equations," J. Phys. Chem. Lett. 6, 3834 (2015).
  5. Zhiqiang Tan, Junchao Xia, Bin W. Zhang, and Ronald M. Levy, " Locally weighted histogram analysis and stochastic solution for large-scale multi-state free energy estimation," J. Chem. Phys. 144, 034107 (2016).