Molecular Docking Improved with Human Spatial Perception Using Virtual Reality.

Area of Science:

• Computational biophysics
• Molecular dynamics simulations
• Drug discovery

Background:

• Adaptive steered molecular dynamics (ASMD) applies external forces to guide molecular motion.
• Virtual reality (VR) offers interactive visualization for molecular dynamics and docking.

Purpose of the Study:

• To develop a novel method guiding ASMD using human-guided trajectories from interactive molecular dynamics in VR (iMD-VR).
• To assess the efficacy of VR-assisted ASMD in expediting protein-ligand binding and improving accuracy.

Main Methods:

• Interactive molecular dynamics in virtual reality (iMD-VR) was used to collect optimal ligand binding trajectories.
• These human-guided trajectories were employed to steer adaptive steered molecular dynamics (ASMD) simulations.
• The performance of iMD-VR-assisted ASMD was compared against standard ASMD simulations.

Main Results:

• iMD-VR-assisted ASMD demonstrated faster and more effective convergence of ligands to protein binding sites.
• The method achieved higher Potential Mean Force (PMF) values, nearly doubling those from standard ASMD.
• Users could guide Amprenavir into HIV-1 protease binding pockets and recreate crystallographic poses within 5 minutes.

Conclusions:

• VR-assisted ASMD is a novel and effective approach for accelerating drug discovery by enhancing ligand binding efficiency and accuracy.
• This method shows significant potential for improving molecular dynamics simulations in drug design.
• Future work will focus on AI algorithms to predict optimal binding trajectories and steering forces.