New Generation of General AMBER Force Field for Biomedical Research

用于生物医学研究的新一代通用琥珀力场

基本信息

  • 批准号:
    10709551
  • 负责人:
  • 金额:
    $ 33.06万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-24 至 2026-08-31
  • 项目状态:
    未结题

项目摘要

New Generation of General AMBER Force Field for Biomedical Research Molecular simulation plays an essential role in biochemical and biophysical research. Its major application is to decipher molecular interactions between small molecule ligands and biomolecules, especially protein receptors, so that highly potent agonists or antagonists can be discovered to enhance or eradicate target functions. Despite tremendous efforts spent on development, it is still very challenging to accurately predict protein-ligand binding. A key element to a successful prediction is the quality of practical molecular mechanics force field (MMFF). From the viewpoint of feasibility, the classical additive force field is in a unique position to offer computational efficiency while maintaining robustness for accurate and automated parametrization, which cannot be easily afforded by a polarizable force field. The other key factor to a successful prediction is the ability of the sampling strategy to effectively sample “hidden” events that are coupled with state transitions. The major goal of this project is to develop and test the 3rd generation of GAFF (GAFF3) to significantly improve the quality of the general- purpose AMBER force fields. GAFF3 will be critically evaluated in studying biomolecule-ligand interactions using a novel GPU-accelerated 𝜆 -dynamics based orthogonal space tempering (OST) algorithm. The advanced sampling technique will guarantee that our macromolecule-ligand binding free energy calculations is not complicated by existing sampling issues so that GAFF3 can be objectively evaluated. We will first develop GAFF3 utilizing ABCG2, a new physical charge model which has demonstrated its superior performance in large scale solvation free energy calculations; New force field parameterization techniques, such as applying ANI-1x potentials to fast detect “bad” torsional parameters, will be extensively applied in GAFF3 development. We will then critically evaluate the GAFF3 performance in studying biomolecule-ligand interactions using both pathway-based and endpoint free energy methods. The OST sampling method will be developed and implemented for this evaluation effort. Last, we plan to apply a variety of strategies to handle “difficult” molecules identified by us or our users. Those strategies will include fine atom typing and introduction of new functional forms. We believe that those efforts will allow GAFF3 to approach the performance limit an additive model could have. We will also expand the chemical space of GAFF3 to cover those elements not covered by the current GAFF, but frequently occurring in drugs and PDB ligands. Therefore, the successful pursuit of these research aims will facilitate us to surmount the challenges in accurately modeling protein-ligand and nucleic acid- ligand binding.
用于生物医学研究的新一代通用琥珀力场 分子模拟在生物化学和生物物理研究中起着至关重要的作用。其主要 应用是破译小分子配体和 生物分子,特别是蛋白质受体,因此可以产生高效的激动剂或拮抗剂 发现增强或消除目标功能。尽管付出了巨大的努力 发展中,准确预测蛋白质-配体结合仍然非常具有挑战性。一把钥匙 成功预测的要素是实用分子力学力场的质量 (MMFF)。从可行性角度来看,经典加性力场具有独特的地位 提供计算效率,同时保持准确和自动化的鲁棒性 参数化,这是极化力场无法轻易实现的。另一个关键因素 成功预测的关键在于采样策略有效采样“隐藏”的能力 与状态转换相结合的事件。该项目的主要目标是开发和 测试第三代GAFF(GAFF3),显着提高通用质量- 目的琥珀力场。 GAFF3 将在生物分子配体研究中受到严格评估 使用新颖的 GPU 加速的 𝜆 -基于动力学的正交空间回火进行交互 (OST)算法。先进的采样技术将保证我们的大分子配体 结合自由能计算并不因现有采样问题而复杂化,因此 GAFF3 可以客观评价。我们将首先利用ABCG2(一种新的物理电荷)开发GAFF3 该模型在大规模溶剂化自由能方面展示了其优越的性能 计算;新的力场参数化技术,例如将 ANI-1x 势应用到 快速检测“坏”扭转参数,将广泛应用于GAFF3开发中。我们将 然后批判性地评估 GAFF3 在研究生物分子-配体相互作用中的性能 基于路径的方法和终点自由能方法。 OST 采样方法为 为此评价工作制定并实施了。最后,我们计划应用多种策略 处理我们或我们的用户识别的“困难”分子。这些策略将包括精细原子 打字和引入新的功能形式。我们相信,这些努力将使 GAFF3 接近附加模型可能具有的性能极限。我们还将扩大化学品 GAFF3 的空间来涵盖当前 GAFF 未涵盖的要素,但经常 发生在药物和 PDB 配体中。因此,成功实现这些研究目标将 帮助我们克服精确建模蛋白质配体和核酸方面的挑战 配体结合。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Junmei Wang其他文献

Junmei Wang的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Junmei Wang', 18)}}的其他基金

AI-Powered Biased Ligand Design
人工智能驱动的偏向配体设计
  • 批准号:
    10637910
  • 财政年份:
    2023
  • 资助金额:
    $ 33.06万
  • 项目类别:
New Generation of General AMBER Force Field for Biomedical Research
用于生物医学研究的新一代通用琥珀力场
  • 批准号:
    10798829
  • 财政年份:
    2022
  • 资助金额:
    $ 33.06万
  • 项目类别:
New Generation of General AMBER Force Field for Biomedical Research
用于生物医学研究的新一代通用琥珀力场
  • 批准号:
    10503886
  • 财政年份:
    2022
  • 资助金额:
    $ 33.06万
  • 项目类别:
Protein Design Using Physical Scoring Functions integrated with Site Couplings
使用与位点耦合集成的物理评分函数进行蛋白质设计
  • 批准号:
    8320949
  • 财政年份:
    2011
  • 资助金额:
    $ 33.06万
  • 项目类别:

相似海外基金

EXCESS: The role of excess topography and peak ground acceleration on earthquake-preconditioning of landslides
过量:过量地形和峰值地面加速度对滑坡地震预处理的作用
  • 批准号:
    NE/Y000080/1
  • 财政年份:
    2024
  • 资助金额:
    $ 33.06万
  • 项目类别:
    Research Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
  • 批准号:
    2328975
  • 财政年份:
    2024
  • 资助金额:
    $ 33.06万
  • 项目类别:
    Continuing Grant
SHINE: Origin and Evolution of Compressible Fluctuations in the Solar Wind and Their Role in Solar Wind Heating and Acceleration
SHINE:太阳风可压缩脉动的起源和演化及其在太阳风加热和加速中的作用
  • 批准号:
    2400967
  • 财政年份:
    2024
  • 资助金额:
    $ 33.06万
  • 项目类别:
    Standard Grant
Market Entry Acceleration of the Murb Wind Turbine into Remote Telecoms Power
默布风力涡轮机加速进入远程电信电力市场
  • 批准号:
    10112700
  • 财政年份:
    2024
  • 资助金额:
    $ 33.06万
  • 项目类别:
    Collaborative R&D
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
  • 批准号:
    2328973
  • 财政年份:
    2024
  • 资助金额:
    $ 33.06万
  • 项目类别:
    Continuing Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
  • 批准号:
    2328972
  • 财政年份:
    2024
  • 资助金额:
    $ 33.06万
  • 项目类别:
    Continuing Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
  • 批准号:
    2332916
  • 财政年份:
    2024
  • 资助金额:
    $ 33.06万
  • 项目类别:
    Standard Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
  • 批准号:
    2332917
  • 财政年份:
    2024
  • 资助金额:
    $ 33.06万
  • 项目类别:
    Standard Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
  • 批准号:
    2328974
  • 财政年份:
    2024
  • 资助金额:
    $ 33.06万
  • 项目类别:
    Continuing Grant
Study of the Particle Acceleration and Transport in PWN through X-ray Spectro-polarimetry and GeV Gamma-ray Observtions
通过 X 射线光谱偏振法和 GeV 伽马射线观测研究 PWN 中的粒子加速和输运
  • 批准号:
    23H01186
  • 财政年份:
    2023
  • 资助金额:
    $ 33.06万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了