Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities.
Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities.
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DOI：
10.1515/jmbm-2013-0024
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发表时间：
2013-12
影响因子：
1.8
通讯作者：
Bardhan JP
中科院分区：
文献类型：
--
作者：
Bardhan JP
为了在模拟材料的研究人员和模拟生物分子的研究人员之间架起一座桥梁，我们综述了研究蛋白质和核酸行为的非局部介电连续介质模型的最新进展。就像在其他科学领域一样，当原子模拟(例如分子动力学)过于昂贵时，连续介质模型是必不可少的工具。由于生物分子基本上都是纳米尺度的系统，涉及局部介电响应的标准连续介质模型基本上一直充其量都是可疑的。这里讨论的高级连续介质理论旨在通过添加诸如非局部介电响应和介电饱和引起的非线性等特性来弥补这些缺点。我们首先在分子尺度上描述静电相互作用在生物学中的中心作用，并利用在科学和工程中的应用来推动计算容易处理的连续介质模型的发展。作为背景，我们强调了仍然存在的一些最重要的挑战，并概述了处理这些挑战的各种理论形式，强调了支持使用和改进连续统模型的严格的统计力学。然后，我们讨论非局部介质模型的开发和实现，这是近40年前由Dogonadze、Kornyshev和他们的合作者开创的一种方法。这些模型中最简单的只是一个标量形式的梯度弹性，这里我们使用基于梯度的建模思想来扩展静电模型，以包括额外的长度比例。论文最后讨论了模型开发的公开问题，强调了材料界利用其物理、数学和计算专业知识帮助解决分子生物学和生物物理学中最具挑战性的问题之一的许多机会。
In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g. molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding features such as nonlocal dielectric response, and nonlinearities resulting from dielectric saturation. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost forty years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The paper concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.