Molecular Dynamics Trajectory Analysis of Permeation (MDTAP): A tool to analyze permeation events across membrane proteins

Abstract Background and Objective Molecular dynamics (MD) simulations are indispensable and versatile in capturing the time-dependent conformational changes of biomolecules to shed light on the concomitant biological processes. MD is used to provide critical mechanistic insights into the transportation of solvent/solute/drug molecules across protein channels embedded in a membrane bilayer. The huge size and volume of the MD trajectories of a membrane-embedded system provide challenges in the analyses of membrane permeation events. Thus, a software, Molecular Dynamics Trajectory Analysis of Permeation (MDTAP), is presented here to analyze the permeation events across membrane-embedded proteins and nucleic acids automatically. Methods A software is developed here to automatically detect the permeation events across the channels irrespective of their shape and size and the type of solute molecules from the MD trajectories. MDTAP employs bash scripts to fetch information about the permeation, residence time, and diffusion of the molecules of interest in a Linux/Mac-based environment. The source code of MDTAP is freely available to the public, along with installation and usage information on GitHub ( attached as supplementary for the review process and will be made accessible to the public through the following link upon acceptance for publication: https://github.com/MBL-lab/MDTAP ). Results The efficiency of MDTAP is demonstrated here by considering the MD trajectories of 2 water-conducting channels as test cases: E. coli outer membrane protein Wzi and E. coli Aquaporin Z. The dimensions of the channels and their capacity to accommodate and conduct water, the number of permeating water molecules along with the path traced and time taken to cross the channel is validated. Conclusion In summary, the graphical representation of the time-dependent behavior of the solute/solvent permeation events corresponding to an MD trajectory in MDTAP allows the user to easily visualize the mechanism of permeation, including the localization of the permeating molecule (if any) and permeating path. Thus, MDTAP immensely reduces the difficult task of manually analyzing solute/solvent permeations from the bulk MD trajectories. Such a simplistic representation of permeation events across the protein transporters helps in the design of drug molecules to treat the associated diseases. Further, MDTAP is also designed to characterize the permeation events across artificial nucleic acid channels, considering their importance in recent times.