Collaborative Research: A new diffuse-interface approach to ensemble average solvation energy: modeling, analysis and computation

协作研究:一种新的整体平均溶剂化能的扩散界面方法:建模、分析和计算

基本信息

项目摘要

In the quantitative analysis of biological processes, the complex interactions between the solute and solvent are typically described by solvation energies: the free energy of transferring the solute or biomolecule (e.g., proteins, DNA, RNA) from the vacuum to a solvent environment of interest (e.g., water at a certain ionic strength). Compared with explicit solvent models, which treat both the solute and the solvent as individual molecules, implicit solvent models, which average the effect of solvent phase as continuum media, are much more efficient and thus can handle much larger systems. Central to the construction of implicit solvent models is an interface separating the solute and solvent domains. However, commonly used interface definitions are ad hoc partitions and thus either non-negligibly overestimate or underestimate the solvation free energies. Variational implicit solvation models (VISM) have emerged as a successful approach to calculate the disposition of the solute-solvent interface by optimizing a solvation energy functional coupling the discrete description of the biomolecule and the continuum description of the solvent. The objective of this collaborative research project is to enhance the precision and computational efficiency of solvation energy prediction by means of VISM. The project will involve novel developments in mathematical models and numerical algorithms that can better reflect the interactions between biological macromolecules and the surrounding ionic environment. In addition, the project will provide opportunities for students to be involved in this collaborative research.Research has shown that neglecting the inherent randomness associated with solute-solvent interfaces, resulting from atom vibrations or thermodynamic fluctuations, can lead to substantial errors in predicting solvation energies. Since experimentally observed solvation energies are ensemble averages, the primary objective of this research is to develop a diffuse-interface VISM capable of capturing the ensemble average solvation energy (EASE). EASE represents the weighted average of solvation energies computed from all possible microstates of the solute-solvent system. In the routine calculation of EASE, one needs to carry out explicit solvent simulations, such as molecular dynamics (MD), to obtain thousands of solute-solvent configurations (snapshots) and perform energy calculations for each snapshot. Leveraging tools from statistical mechanics and geometric measure theory, this project aims to develop an innovative diffuse-interface VISM that rigorously reproduces EASE by utilizing a single diffuse interface profile instead of thousands of individual snapshots. Furthermore, while diffuse-interface VISMs offer improved accuracy compared to implicit solvent models utilizing predetermined interfaces, the computational cost associated with determining the interface poses a significant challenge. This limitation hampers the application of diffuse-interface VISMs to large molecular systems. Therefore, the second goal of this research is to develop accelerated numerical algorithms for solvation energy computation within the framework of diffuse-interface VISMs. By capitalizing on the structure of the proposed diffuse-interface VISM functional, a novel optimization algorithm will be devised that combines the augmented Lagrangian method with an inexact Newton scheme. This innovative approach will markedly enhance computational efficiency. Lastly, the analysis of the proposed model will provide novel techniques for studying the regularity of solutions to total variation minimization problems. The analytic techniques developed within the scope of this research project may also have broader relevance and applicability within the mathematical community.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
在生物过程的定量分析中,溶质和溶剂之间的复杂相互作用通常由溶剂化能描述:转移溶质或生物分子的自由能(例如,蛋白质,DNA,RNA)从真空到感兴趣的溶剂环境(例如,在一定离子强度下的水)。与将溶质和溶剂作为单个分子处理的显式溶剂模型相比,将溶剂相作为连续介质平均的隐式溶剂模型效率更高,因此可以处理更大的系统。隐式溶剂模型的核心是溶质和溶剂域的界面分离。然而,常用的界面定义是特设分区,因此不可忽略高估或低估的溶剂化自由能。变分隐式溶剂化模型(VISM)通过优化耦合生物分子的离散描述和溶剂的连续描述的溶剂化能泛函,已成为计算溶质-溶剂界面的一种成功方法。本合作研究项目的目的是提高溶剂化能预测的精度和计算效率。该项目将涉及数学模型和数值算法的新发展,这些模型和算法可以更好地反映生物大分子与周围离子环境之间的相互作用。此外,该项目将为学生提供参与这项合作研究的机会。研究表明,忽略与溶质-溶剂界面相关的固有随机性,由原子振动或热力学波动引起,可能导致预测溶剂化能的重大错误。由于实验观察到的溶剂化能系综平均,本研究的主要目标是开发一个扩散界面VISM能够捕获系综平均溶剂化能(EASE)。EASE表示从溶质-溶剂系统的所有可能微观状态计算的溶剂化能的加权平均值。在EASE的常规计算中,需要进行明确的溶剂模拟,例如分子动力学(MD),以获得数千个溶质-溶剂配置(快照)并为每个快照执行能量计算。利用统计力学和几何测量理论的工具,该项目旨在开发一种创新的扩散界面VISM,通过利用单个扩散界面轮廓而不是数千个单独的快照来严格再现EASE。此外,虽然与利用预定界面的隐式溶剂模型相比,扩散界面VISM提供了更高的精度,但与确定界面相关的计算成本构成了重大挑战。这一限制阻碍了扩散界面VISMs在大分子体系中的应用。因此,本研究的第二个目标是开发扩散界面VISMs框架内溶剂化能计算的加速数值算法。通过利用所提出的扩散界面VISM泛函的结构,将设计一种新的优化算法,该算法将增广拉格朗日方法与不精确牛顿方案相结合。这种创新的方法将显著提高计算效率。最后,该模型的分析将提供新的技术研究的规律性的总变差最小化问题的解决方案。在本研究项目范围内开发的分析技术也可能在数学界具有更广泛的相关性和适用性。该奖项反映了NSF的法定使命,并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

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 }}

Zhan Chen其他文献

Motion Characteristic Evaluation of an Amphibious Spherical Robot
水陆两栖球形机器人运动特性评估
Iteration-based error compensation for a worn grinding wheel in solid cutting tool flute grinding
整体刀具槽磨削中磨损砂轮的迭代误差补偿
  • DOI:
    10.1016/j.promfg.2019.06.134
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Xianli Liu;Zhan Chen;Wei Ji;Lihui Wang
  • 通讯作者:
    Lihui Wang
Multireflection sum frequency generation vibrational spectroscopy.
多重反射和频产生振动光谱。
  • DOI:
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    7.4
  • 作者:
    Chi Zhang;J. Jasensky;Zhan Chen
  • 通讯作者:
    Zhan Chen
Investigation of Drug-Model Cell Membrane Interactions Using Sum Frequency Generation Vibrational Spectroscopy: A Case Study of Chlorpromazine
使用和频产生振动光谱研究药物模型细胞膜相互作用:氯丙嗪的案例研究
  • DOI:
    10.1021/jp503038m
  • 发表时间:
    2014-07
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Chi Zhang;Xiaofeng Han;Minghu Song;Zhan Chen
  • 通讯作者:
    Zhan Chen
A Powerful Nonlinear Optical Technique to Characterize Surfaces and Interfaces Sum Frequency Generation Vibrational Spectroscopy
一种强大的非线性光学技术来表征表面和界面和频率产生振动光谱
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Xiaolin Lu;Zhan Chen;Xin Ping Wang
  • 通讯作者:
    Xin Ping Wang

Zhan Chen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('Zhan Chen', 18)}}的其他基金

Molecular Structures of Interfacial Proteins Studied by Isotope Labeling and Sum Frequency Generation Vibrational Spectroscopy
同位素标记和和频振动光谱研究界面蛋白的分子结构
  • 批准号:
    1904380
  • 财政年份:
    2019
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Continuing Grant
A Novel Computational Method for Diffuse Interface Models of Implicit Solvation of Biomolecules
生物分子隐式溶剂化扩散界面模型的一种新计算方法
  • 批准号:
    1818748
  • 财政年份:
    2018
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Continuing Grant
Developing a Combined Vibrational Spectroscopic and Optical/Fluorescence Imaging Approach for Simultaneous Orientation and Activity Measurement of Immobilized Biomolecules
开发一种组合振动光谱和光学/荧光成像方法,用于固定生物分子的同步定向和活性测量
  • 批准号:
    1505385
  • 财政年份:
    2015
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Continuing Grant
Molecular Level Studies on Phthalates at Interfaces Using Nonlinear Optical Spectroscopic Techniques
使用非线性光谱技术对界面邻苯二甲酸盐进行分子水平研究
  • 批准号:
    1111000
  • 财政年份:
    2011
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Continuing Grant
CAREER: Developing SFG into a Powerful Ananlytical Technique to Unerstand Molecular Adhension Mechanisms at Polymer Interfaces
职业:将 SFG 发展成为一种强大的分析技术,以了解聚合物界面上的分子粘附机制
  • 批准号:
    0449469
  • 财政年份:
    2005
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Continuing Grant
SFG Studies on Surface Structures of Polymethacrylates in Air, in Water, and Interacting with Protein Molecules
SFG 研究聚甲基丙烯酸酯在空气、水中以及与蛋白质分子相互作用的表面结构
  • 批准号:
    0315857
  • 财政年份:
    2003
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Standard Grant
PostDoctoral Research Fellowship
博士后研究奖学金
  • 批准号:
    0209532
  • 财政年份:
    2002
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Fellowship Award

相似国自然基金

Research on Quantum Field Theory without a Lagrangian Description
  • 批准号:
    24ZR1403900
  • 批准年份:
    2024
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
Cell Research
  • 批准号:
    31224802
  • 批准年份:
    2012
  • 资助金额:
    24.0 万元
  • 项目类别:
    专项基金项目
Cell Research
  • 批准号:
    31024804
  • 批准年份:
    2010
  • 资助金额:
    24.0 万元
  • 项目类别:
    专项基金项目
Cell Research (细胞研究)
  • 批准号:
    30824808
  • 批准年份:
    2008
  • 资助金额:
    24.0 万元
  • 项目类别:
    专项基金项目
Research on the Rapid Growth Mechanism of KDP Crystal
  • 批准号:
    10774081
  • 批准年份:
    2007
  • 资助金额:
    45.0 万元
  • 项目类别:
    面上项目

相似海外基金

Collaborative Research: REU Site: Earth and Planetary Science and Astrophysics REU at the American Museum of Natural History in Collaboration with the City University of New York
合作研究:REU 地点:地球与行星科学和天体物理学 REU 与纽约市立大学合作,位于美国自然历史博物馆
  • 批准号:
    2348998
  • 财政年份:
    2025
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Standard Grant
Collaborative Research: REU Site: Earth and Planetary Science and Astrophysics REU at the American Museum of Natural History in Collaboration with the City University of New York
合作研究:REU 地点:地球与行星科学和天体物理学 REU 与纽约市立大学合作,位于美国自然历史博物馆
  • 批准号:
    2348999
  • 财政年份:
    2025
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Standard Grant
Collaborative Research: New to IUSE: EDU DCL:Diversifying Economics Education through Plug and Play Video Modules with Diverse Role Models, Relevant Research, and Active Learning
协作研究:IUSE 新增功能:EDU DCL:通过具有不同角色模型、相关研究和主动学习的即插即用视频模块实现经济学教育多元化
  • 批准号:
    2315700
  • 财政年份:
    2024
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Standard Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341426
  • 财政年份:
    2024
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Continuing Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341424
  • 财政年份:
    2024
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Continuing Grant
Collaborative Research: On New Directions for the Derivation of Wave Kinetic Equations
合作研究:波动力学方程推导的新方向
  • 批准号:
    2306378
  • 财政年份:
    2024
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Standard Grant
Collaborative Research: AF: Small: New Directions in Algorithmic Replicability
合作研究:AF:小:算法可复制性的新方向
  • 批准号:
    2342244
  • 财政年份:
    2024
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Standard Grant
Collaborative Research: New to IUSE: EDU DCL:Diversifying Economics Education through Plug and Play Video Modules with Diverse Role Models, Relevant Research, and Active Learning
协作研究:IUSE 新增功能:EDU DCL:通过具有不同角色模型、相关研究和主动学习的即插即用视频模块实现经济学教育多元化
  • 批准号:
    2315699
  • 财政年份:
    2024
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Standard Grant
Collaborative Research: Understanding New Labor Relations for the 21st Century
合作研究:理解21世纪的新型劳动关系
  • 批准号:
    2346230
  • 财政年份:
    2024
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Standard Grant
Collaborative Research: New Regression Models and Methods for Studying Multiple Categorical Responses
合作研究:研究多重分类响应的新回归模型和方法
  • 批准号:
    2415067
  • 财政年份:
    2024
  • 资助金额:
    $ 6.49万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了