Breakthrough Molecular Dynamics Research via an Anton2 Supercomputer

通过 Anton2 超级计算机进行突破性分子动力学研究

• 批准号: 10615059
• 负责人: Philip D. Blood
• 金额: $ 38.53万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615059
• 关键词: Academy; Area; Award; Awareness; Binding Proteins; Biological; Biology; Biomedical Research; Collaborations; Communities; Community Health Education; Creativeness; Data; Data Collection; Data Science; Data Set; Disease; Evaluation; FAIR principles; Funding; Gifts; Goals; Grant; Institution; Instruction; Ion Channel; Knowledge; Letters; Machine Learning; Membrane; Molecular; National Research Council; Process; Protocols documentation; Publications; Quality of life; Reporting; Research; Research Personnel; Research Project Grants; Research Support; Resources; Running; Science; Secure; Services; Supercomputing; System; Time; Training Programs; Underrepresented Populations; United States National Academy of Sciences; United States National Institutes of Health; Work; anxious; archive data; base; broadening participation research; computing resources; cost; data management; data mining; data sharing; improved; innovation; molecular dynamics; next generation; outreach; outreach program; price lists; protein folding; service providers; supercomputer; uptake; web portal

Project Summary In 2010, Pittsburgh Supercomputing Center (PSC) and D.E. Shaw Research (DESRES) partnered to make the Anton special-purpose molecular dynamics (MD) supercomputer available to the national biomedical research community for the first time. Anton enabled researchers to simulate biomolecular systems two orders of magnitude faster than any conventional supercomputer, allowing researchers access to critical multi- microsecond and longer timescales on which most biologically-significant molecular processes take place. In 2016, with operational support from NIH, DESRES made available a next generation Anton 2 system at PSC at no cost. This multimillion-dollar gift from DESRES, with NIH support, provided a unique opportunity for researchers to tackle even more groundbreaking biological questions by simulating systems as large as 700,000 atoms at a rate of multiple microseconds per day. The goal of this renewal project is to provide the national biomedical research community with continued access to this unique and powerful Anton 2 resource and to maximize the benefit of this resource to the community. Since 2010, PSC has supported 589 research projects conducted by 202 unique PIs on the Anton systems hosted at PSC. So far, these projects have resulted in 292 publications, many of which have had significant impact on their fields of research. These fields cover the entire spectrum of biomolecular processes that form the fundamental underpinnings of biology, including protein folding, ion channel selectivity and gating, membrane dynamics and organization, protein- ligand binding, and many others. Demand for Anton 2 is quite high, with 2-3x higher demand than can be met each year. Given this, our goals are focused not only on providing continued access but also on maximizing the value of this limited resource to the community—recognizing that the creativity of the broad, diverse Anton 2 research community is one of our most powerful resources for innovation. Anton 2 will be integrated as an XSEDE service provider, and the accessibility and impact of Anton 2 will significantly increase by engaging in their extensive broadening participation, outreach, and training programs. Through these outreach efforts, researchers at many more institutions will have the opportunity to use Anton 2, especially researchers from traditionally underrepresented groups in biomedical research. The hundreds of long-timescale MD trajectories researchers generate on Anton 2 constitute a unique and valuable dataset that can be used to gain additional biomedical knowledge and advance the application of machine learning protocols to augment molecular dynamics simulations. This important dataset will be available to researchers and educators worldwide through a web portal and co-located on the PSC's Bridges-2 system for classroom instruction and research, including reanalysis, machine learning, and data mining.

项目概要 2010 年，匹兹堡超级计算中心 (PSC) 和 D.E. Shaw Research (DESRES) 合作开发了 安东专用分子动力学（MD）超级计算机可用于国家生物医学研究 Anton 社区首次使研究人员能够模拟两个数量级的生物分子系统。 比任何传统超级计算机都要快，使研究人员能够访问关键的多 大多数具有生物学意义的分子过程发生在微秒和更长的时间尺度上。 2016 年，在 NIH 的运营支持下，DESRES 在 PSC 提供了下一代 Anton 2 系统 在 NIH 的支持下，DESRES 提供的这份价值数百万美元的礼物为我们提供了一个独特的机会。 研究人员通过模拟大到以下的系统来解决更具突破性的生物学问题 700,000 个原子，每天数微秒的速度。这个更新项目的目标是提供 国家生物医学研究界可以持续访问这一独特而强大的 Anton 2 资源 自 2010 年以来，PSC 已支持 589 项研究。 到目前为止，这些项目已由 202 个独特的 PI 在 PSC 托管的 Anton 系统上进行。 发表了 292 篇论文，其中许多对其研究领域产生了重大影响。 涵盖构成生物学基础的整个生物分子过程， 包括蛋白质折叠、离子通道选择性和门控、膜动力学和组织、蛋白质- 对 Anton 2 的需求非常高，比可满足的需求高出 2-3 倍。 鉴于此，我们的目标不仅集中于提供持续的访问，而且还集中于最大化。 这种有限资源对社区的价值——认识到广泛、多样化的安东的创造力 2 研究社区是我们最强大的创新资源之一，Anton 2 将被整合为一个。 XSEDE 服务提供商，Anton 2 的可访问性和影响力将通过参与而显着提高 通过这些外展工作，他们广泛扩大了参与、外展和培训计划。 更多机构的研究人员将有机会使用 Anton 2，特别是来自 传统上生物医学研究中代表性不足的群体。数百个长期尺度的 MD 轨迹。 研究人员在 Anton 2 上生成的数据集构成了一个独特且有价值的数据集，可用于获得额外的信息 生物医学知识并推进机器学习协议的应用以增强分子 这个重要的数据集将通过以下方式提供给全世界的研究人员和教育工作者。 一个门户网站，位于 PSC 的 Bridges-2 系统上，用于课堂教学和研究，包括 再分析、机器学习和数据挖掘。

项目成果

The Molecular Mechanism of P2Y1 Receptor Activation.

P2Y1 受体激活的分子机制。

• 发表时间: 2016-08-22
• 作者: Yuan, Shuguang;Chan, H C Stephen;Vogel, Horst;Filipek, Slawomir;Stevens, Raymond C;Palczewski, Krzysztof
• 通讯作者: Palczewski, Krzysztof

Kinesin motility is driven by subdomain dynamics.

驱动蛋白运动由子域动力学驱动。

• 发表时间: 2017
• 影响因子: 7.7
• 作者: Hwang, Wonmuk;Lang, Matthew J;Karplus, Martin
• 通讯作者: Karplus, Martin

Investigating Small-Molecule Ligand Binding to G Protein-Coupled Receptors with Biased or Unbiased Molecular Dynamics Simulations.

通过有偏或无偏分子动力学模拟研究小分子配体与 G 蛋白偶联受体的结合。

• 发表时间: 2018
• 作者: Marino, Kristen A;Filizola, Marta
• 通讯作者: Filizola, Marta

Computed Free Energies of Peptide Insertion into Bilayers are Independent of Computational Method.

计算的肽插入双层的自由能与计算方法无关。

• 发表时间: 2018
• 作者: Gumbart, James C;Ulmschneider, Martin B;Hazel, Anthony;White, Stephen H;Ulmschneider, Jakob P
• 通讯作者: Ulmschneider, Jakob P

Molecular dynamics simulations of an engineered T4 lysozyme exclude helix to sheet transition, and provide insights into long distance, intra-protein switchable motion.

工程 T4 溶菌酶的分子动力学模拟排除了螺旋到片层的转变，并提供了对长距离、蛋白质内可切换运动的见解。

• 发表时间: 2020-02
• 作者: Biggers, Laurence;Elhabashy, Hadeer;Ackad, Edward;Yousef, Mohammad S
• 通讯作者: Yousef, Mohammad S