Multi-scale simulation methods for energy transduction and macromolecular assembly

能量转换和大分子组装的多尺度模拟方法

• 批准号: 1664906
• 负责人: Qiang Cui
• 金额: $ 45万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1664906&HistoricalAwards=false
• 关键词: Multi; scale; simulation; methods; energy

Qiang Cui, of the University of Wisconsin, is supported by an award from the Chemical Theory, Models and Computational Methods program to develop effective molecular simulation methodologies to tackle important and challenging biophysical and chemical problems that involve multiple length scales. The award is cofunded by the Biophysics Program in the Division of Molecular and Cellular Biology. Bioenergy transduction, a type of energy transport in which the form of the energy also changes, is one of the most fascinating aspects of life. Biomolecular motors and pumps transduce energy from one form to the other with remarkable efficiency. The study of energy transduction in biomolecular ion pumps involves developing quantum mechanical and classical models that properly describe the energetics and efficiency of ion transport through the interior of a transmembrane protein. The problem of macromolecular assembly, which underlies many fascinating biological processes such as the formation of muscle fiber, requires the development of effective coarse-grained models that strike the balance of computational efficiency and biophysical specificity. The project offers research opportunities for students at all levels who wish to work at the intersection of chemistry, biology and engineering. Dr. Cui is actively engaged with programs aimed at broadening participation in physical and biological science by members of under-represented minorities.For the problem of ion pumping, by adopting the minimum free energy path approach and a multi-layer Quantum Mechanics/Molecular Mechanics (QMMM) model, Cui and co-workers can significantly improve the accuracy and sampling for the study of long-range proton transfers in complex biomolecules compared to previous efforts. By adopting the chemical potential equalization scheme to represent the polarization of different QM regions, they can properly describe ion transport through the interior of a transmembrane protein that is rich in polar and charged motifs. This computational framework represents the first attempt to include the membrane potential in QM/MM type of simulations. For the problem of coiled-coil assembly, which describes a broad class of problems in which the proper assembly of biomolecules relies critically on a limited degree of flexibility in their structures, their proposed multipolar coarse-grained model makes a natural connection between atomistic and coarse-grained representations with a transparent framework for parameterization. Compared to continuum mechanics models, this model can access similar length and time scales but can be efficiently studied using standard molecular simulation software.

威斯康星大学的崔强（Qiang Cui）获得了化学理论、模型和计算方法项目的奖励，致力于开发有效的分子模拟方法，以解决涉及多个长度尺度的重要和具有挑战性的生物物理和化学问题。该奖项是由分子和细胞生物学部门的生物物理学项目共同资助的。生物能量转导是一种能量传输，其中能量的形式也会发生变化，是生命中最迷人的方面之一。生物分子马达和泵以惊人的效率将能量从一种形式转化为另一种形式。生物分子离子泵中能量转导的研究涉及发展量子力学和经典模型，这些模型适当地描述了离子通过跨膜蛋白质内部传输的能量学和效率。大分子组装问题是许多迷人的生物过程（如肌肉纤维的形成）的基础，需要开发有效的粗粒度模型，以达到计算效率和生物物理特异性的平衡。该项目为希望在化学、生物学和工程学交叉领域工作的各级学生提供了研究机会。崔博士积极参与旨在扩大未被充分代表的少数民族成员参与物理和生物科学的项目。对于离子泵送问题，Cui和同事采用最小自由能路径方法和多层量子力学/分子力学（QMMM）模型，与以往的研究相比，可以显著提高复杂生物分子中远程质子转移研究的准确性和采样率。通过采用化学势均衡方案来表示不同QM区域的极化，它们可以很好地描述离子通过富含极性和带电基序的跨膜蛋白内部的传输。这个计算框架代表了首次尝试将膜电位包括在QM/MM类型的模拟中。对于线圈组装的问题，它描述了一类广泛的问题，其中生物分子的适当组装严重依赖于其结构的有限程度的灵活性，他们提出的多极粗粒度模型在原子和粗粒度表示之间建立了自然联系，具有透明的参数化框架。与连续介质力学模型相比，该模型可以获得相似的长度和时间尺度，但可以使用标准的分子模拟软件进行有效的研究。

项目成果

Network analysis of a proposed exit pathway for protons to the P-side of cytochrome c oxidase

• DOI: 10.1016/j.bbabio.2018.05.010
• 发表时间: 2018-10-01
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
• 影响因子: 4.3
• 作者: Cai, Xiuhong;Haider, Kamran;Gunner, M. R.
• 通讯作者: Gunner, M. R.