A virtual reality environment for interactive biomolecular drug discovery

用于交互式生物分子药物发现的虚拟现实环境

• 批准号: 1793001
• 金额: --
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1793001
• 关键词: virtual; reality; environment; interactive; biomolecular

Molecular simulation constitutes an indispensable tool in both understanding and designing biochemical archi-tectures.Because it furnishes microscopic understanding into a wide range of diseases at the molecular scale, it ena-bles us to designtargeted pharmaceutical remedies to tackle disease at the nano-scale. Drug design problems are effectively problems of'shape-matching' - i.e., designing a small molecular ligand (a drug) that fits snugly into a larger molecular receptor (a protein) -a sort of "3d molecular Tetris". One of the biggest challenges in this design process arises from the fact that biomolecularsystems are flexible objects with thousands of degrees of freedom: there is a massive range of different shapes to considerduring drug design. To tackle this complexity, biomolecular scientists typically use the following approach: they assume thatbiomolecules are rigid, and they use 'blind-search' algorithms to search the high-dimensional space of possible fits betweenligand and receptor.Recent work at the frontiers of HCI and molecular simulation has begun to investigate another strategy to tackle this searchproblem: interactive molecular simulation (iMS). The idea of iMS is that a well-designed human-computer interface offers theopportunity for expert human intuition to 'guide' blind search algorithms, effectively combining the high-level reasoning abilitiesof humans with the brute force compute power of modern HPC architec-tures. Initial results assessing the performance of iMStools have shown that they allow for much more efficient searching than 'blind-search' algorithms alone. Dr. David Glowacki'sgroup has been at the vanguard of iMS platform development, and has recently developed a prototype for a fully interactivemolecular simulation environment that works in the new class of emerging VR technologies, allowing for real-time 3dmanipulation of biomolecular dynam-ics simulations.In this project, PhD candidate Helen Deeks will experiment with and develop this prototype iMS VR environment further, andinvestigate how to transform it into an effective platform for designing drugs at the molecular nano-scale. The initial applicationwill focus on developing pharmaceutical remedies for malaria, a domain where Prof. Richard Sessions (Dept of Biochemistry)has significant expertise and has offered his enthusiastic support. Specifi-cally, Helen's VR development activities will focus oninteractively designing drug molecules to inhibit the lactate dehydrogenase enzyme, which is key to killing the parasiteresponsible for cerebral malaria. Successful execution of this project will benefit from expertise across a range of disciplines,and thus has potentially wide impact across computer science, biochemistry, and health. This project will lead to outputs inboth the HCI research community and the biochemistry research community.

分子模拟是理解和设计生物化学体系结构不可或缺的工具，因为它将微观理解扩展到分子尺度上的各种疾病，它使我们能够在纳米尺度上设计有针对性的药物治疗方案来对付疾病。药物设计问题实际上是“形状匹配”问题，即，设计一种小分子配体（一种药物），与更大的分子受体（一种蛋白质）紧密配合--一种“3d分子俄罗斯方块”。这个设计过程中最大的挑战之一来自于这样一个事实，即生物分子系统是具有数千个自由度的柔性物体：在药物设计过程中，有大量不同的形状需要设计。为了解决这种复杂性，生物分子科学家通常使用以下方法：他们假设生物分子是刚性的，并使用“盲搜索”算法来搜索配体和受体之间可能匹配的高维空间。最近在HCI和分子模拟前沿的工作已经开始研究另一种解决这个搜索问题的策略：交互式分子模拟（iMS）。iMS的理念是，一个精心设计的人机界面为专家的直觉提供了“指导”盲搜索算法的机会，有效地将人类的高级推理能力与现代HPC架构的蛮力计算能力结合起来。评估iMSTools性能的初步结果表明，它们允许比单独的“盲搜索”算法更有效的搜索。大卫Glowacki博士的小组一直在iMS平台开发的先锋，并最近开发了一个原型的完全交互式分子模拟环境，在新兴的虚拟现实技术的新类工作，允许实时三维操纵生物分子动力学模拟。在这个项目中，博士候选人海伦Deeks将实验和开发这个原型iMS虚拟现实环境进一步，并研究如何将其转化为在分子纳米尺度上设计药物的有效平台。最初的申请将集中在开发疟疾药物治疗上，这是一个领域，Richard Sessions教授（生物化学系）拥有重要的专业知识，并提供了热情的支持。具体来说，Helen的VR开发活动将集中在交互式设计药物分子以抑制乳酸脱氢酶，这是杀死脑型疟疾寄生虫的关键。该项目的成功执行将受益于一系列学科的专业知识，从而对计算机科学，生物化学和健康产生潜在的广泛影响。该项目将导致HCI研究社区和生物化学研究社区的产出。

项目成果

Sampling molecular conformations and dynamics in a multiuser virtual reality framework.

• DOI: 10.1126/sciadv.aat2731
• 发表时间: 2018-06
• 期刊: Science advances
• 影响因子: 13.6
• 作者: O'Connor M;Deeks HM;Dawn E;Metatla O;Roudaut A;Sutton M;Thomas LM;Glowacki BR;Sage R;Tew P;Wonnacott M;Bates P;Mulholland AJ;Glowacki DR
• 通讯作者: Glowacki DR

Teaching Enzyme Catalysis Using Interactive Molecular Dynamics in Virtual Reality

• DOI: 10.1021/acs.jchemed.9b00181
• 发表时间: 2019-11-01
• 期刊: JOURNAL OF CHEMICAL EDUCATION
• 影响因子: 3
• 作者: Bennie, Simon J.;Ranaghan, Kara E.;Glowacki, David R.
• 通讯作者: Glowacki, David R.