Adaptive steered molecular dynamics (ASMD) is a computational biophysics method in which an external force is applied to a selected set of atoms or a specific reaction coordinate to induce a particular molecular motion. Virtual reality (VR) based methods for protein-ligand docking are beneficial for visualizing on-the-fly interactive molecular dynamics and performing promising docking trajectories. In this paper, we propose a novel method to guide ASMD with optimal trajectories collected from human experiences using interactive molecular dynamics in virtual reality (iMD-VR). We also explain the benefits of using VR as a tool for expediting the process of ligand binding, outlining an experimental protocol that enables iMD-VR users to guide Amprenavir into and out of the binding pockets of HIV-1 protease and recreate their respective crystallographic binding poses within 5 minutes. Later, we discuss our analysis of the results from iMD-VR-assisted ASMD simulation and assess its performance compared to a standard ASMD simulation. From the accuracy point of view, our proposed method calculates higher Potential Mean Force (PMF) values consistently relative to a standard ASMD simulation with an almost twofold increase in all the experiments. Finally, we describe the novelty of the research and discuss results showcasing a faster and more effective convergence of the ligand to the protein's binding site as compared to a standard molecular dynamics simulation, proving the effectiveness of VR in the field of drug discovery. Future work includes the development of an artificial intelligence algorithm capable of predicting optimal binding trajectories for many protein-ligand pairs, as well as the required force needed to steer the ligand to follow the said trajectory.

中文翻译：

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使用虚拟现实改善人类空间感知的分子对接

自适应引导分子动力学（ASMD）是一种计算生物物理学方法，其中将外力施加到选定的一组原子或特定的反应坐标以诱导特定的分子运动。基于虚拟现实 (VR) 的蛋白质-配体对接方法有利于可视化动态交互式分子动力学并执行有希望的对接轨迹。在本文中，我们提出了一种利用虚拟现实中的交互式分子动力学（iMD-VR）从人类经验中收集的最佳轨迹来引导 ASMD 的新方法。我们还解释了使用 VR 作为加速配体结合过程的工具的好处，概述了一个实验方案，使 iMD-VR 用户能够引导安普那韦进出 HIV-1 蛋白酶的结合袋，并重新创建其各自的晶体学结合5 分钟内摆好姿势。随后，我们讨论了对 iMD-VR 辅助 ASMD 模拟结果的分析，并评估其与标准 ASMD 模拟相比的性能。从准确性的角度来看，我们提出的方法相对于标准 ASMD 模拟始终计算出更高的潜在平均力 (PMF) 值，在所有实验中几乎增加了一倍。最后，我们描述了该研究的新颖性，并讨论了与标准分子动力学模拟相比，配体更快、更有效地收敛到蛋白质结合位点的结果，证明了 VR 在药物发现领域的有效性。未来的工作包括开发一种人工智能算法，能够预测许多蛋白质-配体对的最佳结合轨迹，以及引导配体遵循所述轨迹所需的力。