Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
MDTRA: Unified Approach to Molecular Dynamics Data Preparation and Analysis
Molecular dynamics (MD) computation is an extremely informative approach to deep understanding of biological systems at the molecular scale. The principal steps of an MD experiment include preparation of structural files for biological macromolecules and their complexes, fitting optimal conditions and modeling parameters, MD computation, and analysis of the resulting trajectories. There is an imposing number of high-quality MD software packages available (AMBER, NAMD, Gromacs, etc.), yet the field lacks generally accepted integrated approaches to the other workflow stages. Development of Molecular Dynamics Trajectory Reader and Analyzer (MDTRA) software became an endeavor of unifying and systematizing the best MD structure preparation and analysis practices (Popov et al., 2013). The program architecture is based on the principles of ergonomics and augmentability, not requiring explicit scripting (yet supporting it); the ability to rapidly visualize analyzed data; and minimizing system (in particular, RAM) requirements. Working with trajectories as PDB file sets, it allows the user to extract, compute and plot data, compare trajectories using various criteria, and massively analyze such time-dependent values as hydrogen bond energies and DNA helical parameters. An internal visualization module enables a fast preview of any fragment of an MD trajectory. MDTRA proved useful to analyze MD trajectories of DNA repair enzymes (Popov et al., 2013; Lukina et al., 2013), DNA oligomers, etc. Here we report advances in the application of MDTRA for model preparation before a production MD run. New generation implicit solvent models are gaining popularity due to the higher structure mobility and the ability to sample wider conformational space than in the explicit solvent. However, to assess the molecular effects accurately, tightly bound water molecules should be modeled explicitly. We have developed an algorithm, implemented in an MDTRA module, to detect such molecules and minimize their amount, resulting in combined implicit/explicit solvent starting structures. Their MD runs usually demonstrates lower r.m.s.d. and higher stability, as shown in the Figure for bovine pancreatic trypsin inhibitor.
This research has been supported by the grants from Russian Foundation for Basic Research #14-04-01879 and Russian Science Foundation #14-24-00093.
Lukina M. V., Popov A. V., Koval V. V., Vorobjev Y. N., Fedorova O. S. & Zharkov D. O. (2013). DNA damage processing by human 8-oxoguanine-DNA glycosylase mutants with the occluded active site. J. Biol. Chem. 288, 28936-28947.
Alexander V. Popov
SB RAS Institute of Chemical Biology and Fundamental Medicine