Elucidation of protein–ligand interactions by multiple trajectory analysis methods

Abstract

The identification of interaction between protein and ligand including binding positions and strength plays a critical role in drug discovery. Molecular docking and molecular dynamics (MD) techniques have been widely applied to predict binding positions and binding affinity. However, there are few works that describe the systematic exploration of the MD trajectory evolution in this context, potentially leaving out important information. To address the problem, we build a framework, Moira (molecular dynamics trajectory analysis), which enables automating the whole process ranging from docking, MD simulations and various analyses as well as visualizations. We utilized Moira to analyze 400 MD simulations in terms of their geometric features (root mean square deviation and protein–ligand interaction profiler) and energetics (molecular mechanics Poisson–Boltzmann surface area) for these trajectories. Finally, we demonstrate the performance of different analysis techniques in distinguishing native poses among four poses.