DROIDS 1.0 – a GUI-based pipeline for GPU-accelerated comparative protein dynamics — Greg Babbitt

Traditional informatics in comparative genomics and molecular evolution work only with static representations of biomolecules (i.e. sequence and structure), thereby ignoring the molecular dynamics (MD) of proteins that defines function in the cell. A comparative approach applied to MD would connect this very short time scale process, defined in femtoseconds, to one of the longest in the universe, measured in millions of years. Here, we leverage advances in GPU-accelerated molecular dynamics simulation software to develop a comparative method of MD analysis and visualization that can be applied to any two homologous PDB structures. Our open source pipeline, DROIDS (Detecting Relative Outlier Impacts in Dynamic Simulations) works in conjunction with existing molecular modeling software to convert any Linux gaming PC into a ‘comparative computational microscope’ for observing the biophysical effects of mutations and other chemical changes in proteins. DROIDS implements structural alignment and Benjamini-Hochberg corrected Kolmogorov-Smirnov statistics to compare atom bond fluctuations (i.e. thermostability) and correlations in atom vector trajectories (i.e. concerted motions) on the protein backbone, color mapping the significant differences identified in protein MD with single amino acid resolution. DROIDS is simple to use, incorporating separate GUI controls for Amber16 MD simulation, cpptraj analysis and the final statistical and visual representations using both R graphics and UCSF Chimera. DROIDS can also potentially be utilized to visually investigate quantitative changes in molecular dynamics due to binding interactions of pharmaceuticals, toxins, or other biomolecules. Visit our code repository at https://github.com/gbabbitt/DROIDS-1.0 and for many case examples, visit our YouTube channel at https://www.youtube.com/channel/UCJTBqGq01pBCMDQikn566Kw