Unified long-range electrostatics and dynamic protonation for realistic biomolecular simulations on the Exascale
In this DFG supported project we target a flexible, portable and scalable solver for potentials and forces, which is a prerequisite for exascale applications in particle-based simulations with long-range interactions in general. As a particularly challenging example that will prove and demonstrate the capability of our concepts, we use the popular molecular dynamics (MD) simulation software GROMACS. MD simulation has become a crucial tool to the scientific community, especially as it probes time- and length scales difficult or impossible to probe experimentally. Moreover, it is a prototypic example of a general class of complex multiparticle systems with long-range interactions.
MD simulations elucidate detailed, time-resolved behaviour of biology’s nanomachines. From a computational point of view, they are extremely challenging for two main reasons. First, to properly describe the functional motions of biomolecules, the long-range effects of the electrostatic interactions must be explicitly accounted for. Therefore, techniques like the particle-mesh Ewald method were adopted, which, however, severely limits the scaling to a large number of cores due to global communication requirements. The second challenge is to realistically describe the time-dependent location of (partial) charges, as e.g. the protonation states of the molecules depend on their time-dependent electrostatic environment. Here we address both tighly interlinked challenges by the development, implementation, and optimization of a unified algorithm for long-range interactions that will account for realistic, dynamic protonation states and at the same time overcome current scaling limitations.
GROMACS is an open-source software package for molecular simulations, with special focus on offering high performance on a wide-variety of HPC platforms.
The growing variety and heterogeneity of the hardware platforms that need to be supported requires changes in code design. Therefore, recent improvements of the C++ language and how to exploit them for code portability and maintainability are discussed in this workshop. Moreover, advanced user lessons assist with hardware purchases that optimally fit the intended application and the available budget and simulation setup for maximum performance on a given HPC system. Besides hardware variety, also the number of practically relevant molecular mechanics force fields and simulation methods is growing. Recently, GROMACS has been extended to allow incorporation of experimental data from spectroscopy, crystallography and cryo-electron microscopy. An important workshop aim is also an agreement on standardized file formats and data annotation (e.g., experimental conditions, units of measured quantities) for reproducible and transferable use of experimental data. GROMACS has grown to a large-scale collaborative open source software project, which adds challenges in human resource management to the technological challenges. Questions of code maintainability, long-term support of features, code review, coding style are openly discussed.
S. Donnini, T. Ullmann, G. Groenhof, and H. Grubmüller, "Charge-neutral constant pH molecular dynamics simulations using a parsimonious proton buffer.," Journal of Chemical Theory and Computation 12 (3), 1040-1051 (2016).
S. Páll, M. J. Abraham, C. Kutzner, B. Hess, and E. Lindahl, "Tackling exascale software challenges in molecular dynamics simulations with GROMACS.", in Solving Software Challenges for Exascale: International Conference on Exascale Applications and Software, EASC 2014, Stockholm, Sweden, April 2-3, 2014, Revised Selected Papers, edited by S. Markidis and E. Laure (Springer , Cham, 2015), pp. 3-27.
Portable Node-Level Performance Optimization for the Fast Multipole Method
Lecture Notes in Computational Science and Engineering 105, 29-46 (2015)
C. Kutzner, S. Páll, M. Fechner, A. Esztermann, B. de Groot, and H. Grubmüller, "Best bang for your buck: GPU nodes for GROMACS biomolecular simulations.," Journal of Computational Chemistry 36 (26), 1990-2008 (2015).
C. Kutzner, R. Apostolov, B. Hess, and H. Grubmüller, "Scaling of the GROMACS 4.6 molecular dynamics code on SuperMUC.", in Parallel Computing: Accelerating Computational Science and Engineering (CSE), edited by M. Bader, A. Bode, and H. J. Bungartz (IOS Press , Amsterdam, 2014), pp. 722-730.
Comparison of scalable fast methods for long-range interactions
Phys. Rev. E 88 063308-1-22 (2013)
GMCT: A Monte Carlo simulation package for macromolecular receptors
Journal of Computational Chemistry 33, 887-900 (2012)
S. Donnini, F. Tegeler, G. Groenhof, and H. Grubmüller, "Constant pH molecular dynamics in explicit solvent with lambda-dynamics.," Journal of Chemical Theory and Computation 7 (6), 1962-1978 (2011).