DROIDS 1.20: A GUI-Based Pipeline for GPU-Accelerated Comparative Protein Dynamics.

Area of Science:

• Computational Biology
• Genomics
• Biophysics

Background:

• Traditional comparative genomics analyzes static biomolecular data, neglecting crucial molecular dynamics (MD) that dictate protein function.
• Bridging the gap between femtosecond-scale MD and millions of years of molecular evolution is essential for understanding protein function and evolution.

Purpose of the Study:

• To develop a novel comparative method for analyzing and visualizing protein molecular dynamics.
• To create an open-source pipeline, DROIDS, enabling the study of biophysical effects of mutations and chemical changes in homologous proteins.

Main Methods:

• Leveraging graphics-processing-unit-accelerated MD simulations and established molecular modeling software.
• Implementing structural alignment and Benjamini-Hochberg-corrected Kolmogorov-Smirnov statistics for comparing protein backbone fluctuations.
• Utilizing a graphical user interface for Amber16 MD simulations, cpptraj analysis, and visualization in R graphics and UCSF Chimera.

Main Results:

• The DROIDS pipeline successfully compares nanosecond-scale atom bond fluctuations in homologous protein structures.
• Significant differences in protein MD are color-mapped with single-amino-acid resolution, providing visual insights.
• Demonstrated utility in investigating molecular evolution, disease-related functional changes, and potential pharmaceutical binding interactions.

Conclusions:

• DROIDS transforms personal computers into 'comparative computational microscopes' for protein dynamics analysis.
• The pipeline facilitates the visual investigation of the functional and evolutionary impacts of genetic and epigenetic modifications.
• DROIDS offers a powerful tool for exploring protein behavior in a functional evolutionary context.