DynSyst_Special_Topics: Dynamics and Control of Bio-molecular Systems using Geometric Model Reduction and Stochastic Variational Integrators.

DynSyst_Special_Topics：使用几何模型简化和随机变分积分器的生物分子系统动力学和控制。

• 批准号: 0926001
• 负责人: Houman Owhadi
• 金额: $ 45万
• 依托单位: California Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0926001&HistoricalAwards=false
• 关键词: DynSyst_Special_Topics; Dynamics; Control; Bio; molecular

The proposed research will develop novel geometric model reduction methods along with computational methods for the dynamical simulation and eventual control of stochastic mechanical systems involving multiple-scales. These new dynamical and simulation tools will be applied to specific molecular and biomolecular systems. An exciting development in geometric model reduction has been the development of the radii of gyration as coarse variables along with the discovery of specific fine variables that act as triggers that induce conformation changes. A further development of and deeper understanding of such triggers will be important in the eventual control of biomolecular conformation changes and reactions. Going along with these geometric model reduction techniques is the theoretical and computational development of stochastic asynchronous variational integration methods and their applications to the simulation and control of stochastic mechanical systems spanning many temporal-scales.Structure-preserving integrators for stochastic multiscale Hamiltonian systems (possibly with constraints) characterized by multiple time scales and a large number of degrees of freedom are in great demand in computational chemistry, molecular dynamics and biophysics. The proposed work will have a direct and substantial impact on those fields by integrating a new class algorithms in the classical molecular dynamics open source code LAMMPS. Bio-molecules are in general robust to noise; at the same time, these molecules may be responsive to low energy structured actuation. By allowing for the computation of these organized mechanisms, the proposed research will facilitate the development of a new paradigm and novel experimental methods for the control and design of bio-molecules. The proposed research through the identification of resonant frequencies of molecules specific to the membrane of malignant cells and/or known pathogens has the potential to facilitate the discovery and development of a new class of non-invasive and nontoxic therapies. New cancer therapies based on the injection and electro-magnetic excitation of carbon or gold nanotubes/nanorods are already at the clinical trial stage.

这项研究将开发新的几何模型降阶方法和计算方法，用于多尺度随机机械系统的动态模拟和最终控制。这些新的动力学和模拟工具将应用于特定的分子和生物分子系统。几何模型简化方面的一个令人兴奋的发展是，旋转半径作为粗略变量的发展，以及作为引发构象变化的触发因素的特定细变量的发现。对这些触发因素的进一步发展和深入了解将对生物分子构象变化和反应的最终控制具有重要意义。随之而来的是随机异步变分积分方法的理论和计算发展，以及它们在跨越多个时间尺度的随机力学系统的仿真和控制中的应用。具有多时间尺度和大量自由度的随机多尺度哈密顿系统(可能带有约束)的保结构积分器在计算化学、分子动力学和生物物理学中有很大的需求。通过在经典分子动力学开源代码LAMMPS中集成一类新的算法，所提出的工作将对这些领域产生直接和实质性的影响。生物分子通常对噪音很强；同时，这些分子可能会对低能量的结构激励做出反应。通过计算这些有组织的机制，拟议的研究将促进生物分子控制和设计的新范式和新实验方法的发展。通过鉴定恶性细胞膜和/或已知病原体的膜特异性分子的共振频率，这项拟议的研究有可能促进一类新的非侵入性和无毒疗法的发现和开发。基于注射和电磁激发碳或金纳米管/纳米棒的新癌症疗法已经处于临床试验阶段。