BM62015/10.26125/q7f7-zq39

Method development for classical molecular dynamics simulations: coarse-graining and free energy calculations

Author(s): Sereina Riniker

Publication: Bunsenmagazin, Issue 6 2015, Aspekte, Seiten: 228 - 231

Publisher: Deutsche Bunsen-Gesellschaft für physikalische Chemie e.V., Frankfurt

Language: English

DOI: 10.26125/q7f7-zq39

 

Introduction

In classical molecular dynamics (MD) simulations, atoms in molecules are described as (partial) point charges in space, which move in discrete time steps based on Newton’s equations of motion. The strength of MD simulations lies in the investigation of the dynamics of relatively large systems such as proteins, membranes, sugars and other complex (bio)molecular systems, which are not accessible by quantum-mechanical (QM) calculations. Furthermore, important quantities such as free energies of solvation, relative free energies of ligand-protein binding, and conformational free-energy differences can be estimated using MD-based methods. Both, the development of methods for MD simulations and their application domains, are strongly coupled to the advances in computer power. In 1977, the simulation of bovine pancreatic trypsin inhibitor (BPTI) in vacuum was 8.8 picoseconds long [1]. 32 years later, the same protein was simulated in explicit water for one millisecond, i.e. eight orders of magnitude longer, on a special-purpose supercomputer [2]. Despite these advances some of the biggest challenges in MD simulations remain and require further development, especially regarding the quality of force fields, sufficient sampling, accurate estimation of free-energy differences, and increase of computational efficiency to access even larger time and spatial scales with higher accuracy. In this article, we will highlight recent work by us in two of these areas: (i) coarse-graining, which is a method to increase computational speed by reducing the number of particles in the system and by smoothening the energy landscape, and (ii) enveloping distribution sampling, which is a method to estimate free-energy differences without the specification of a pathway.

 

Cite this: Sereina Riniker (2015): Method development for classical molecular dynamics simulations: coarse-graining and free energy calculations. Bunsenmagazin 2015, 6: 228-238. Frankfurt am Main: Deutsche Bunsen-Gesellschaft für physikalische Chemie e.V. DOI: 10.26125/q7f7-zq39

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