Comparison of GPU-accelerated Molecular Dynamics Simulation Efficiency for the Acetylcholinesterase-Huprine X Complex using YASARA, GROMACS, and AMBER

Abstract

Molecular dynamics simulations are a valuable tool in identifying potential acetylcholinesterase inhibitors for Alzheimer's disease therapy. Recent advancements in hardware and software, particularly the implementation of graphics processing units (GPUs), have significantly improved the efficiency of MD simulations. This study aims to compare GPU-accelerated molecular dynamics (MD) simulations of the acetylcholinesterase-Huprine X complex using YASARA, GROMACS, and AMBER. The complex was obtained from Protein Data bank with code 1E66 and was prepared with same conditions. MD simulations were performed for 50 ns with three replicates per software. GROMACS exhibited the shortest average simulation duration (45,104 seconds), followed by AMBER (48,884 seconds) and YASARA (649,208 seconds). RMSD analysis of protein backbone and ligand movement indicated stable simulations across all platforms. Interaction analysis at 25 ns and 35 ns of YASARA’s run revealed that Huprine X maintained key aromatic interactions within the AChE binding pocket, despite undergoing a 180° rotation. YASARA proved more efficient in MD preparation and produced more precise results, while GROMACS was most efficient in simulation runtime. The study highlights the trade-offs between ease of use, simulation speed, and result consistency among these software packages for AChE-HUX MD simulations.