Challenges in structural approaches to cell modeling.
Challenges in structural approaches to cell modeling.
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DOI：
10.1016/j.jmb.2016.05.024
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发表时间：
2016-07-31
影响因子：
5.6
通讯作者：
Vakser IA
中科院分区：
文献类型：
--
作者：
Im W;Liang J;Olson A;Zhou HX;Vajda S;Vakser IA
计算模型对于广泛尺度的生物分子机制的结构表征至关重要。对生物分子机制的充分理解本质上涉及我们对其建模的能力。单个生物分子及其相互作用的结构建模正在迅速进展。然而，从更广泛的角度来看，焦点正在转向更大的系统，直至细胞水平。这种建模涉及在拥挤的细胞环境中更动态、更真实地表示体内相互作用组，以及膜和膜蛋白以及其他细胞成分。细胞的结构建模补充了基于微分方程、图模型和其他技术来建模生物网络、成像数据等的细胞机制的计算方法。结构建模以及其他计算和实验方法将在分子水平上提供对生命的基本理解，并在生物学和医学领域产生重要的应用。本综述中提出的不同方法的横截面说明了从单个分子的结构建模到细胞生物学的结构建模的发展转变。涵盖几个相关领域的研究：生物网络；使用实验数据自动构建三维细胞模型；蛋白质复合物建模；预测非特异性和瞬时蛋白质相互作用；拥挤的热力学和动力学效应；细胞膜建模；和染色体建模。该综述对细胞生物学结构建模各个方面的当前最新技术水平以及这一新兴领域的未来发展前景提出了专家意见。
Computational modeling is essential for structural characterization of biomolecular mechanisms across the broad spectrum of scales. Adequate understanding of biomolecular mechanisms inherently involves our ability to model them. Structural modeling of individual biomolecules and their interactions has been rapidly progressing. However, in terms of the broader picture, the focus is shifting toward larger systems, up to the level of a cell. Such modeling involves a more dynamic and realistic representation of the interactomes in vivo, in a crowded cellular environment, as well as membranes and membrane proteins, and other cellular components. Structural modeling of a cell complements computational approaches to cellular mechanisms based on differential equations, graph models, and other techniques to model biological networks, imaging data, etc. Structural modeling along with other computational and experimental approaches will provide a fundamental understanding of life at the molecular level and lead to important applications to biology and medicine. A cross section of diverse approaches presented in this review illustrates the developing shift from the structural modeling of individual molecules to that of cell biology. Studies in several related areas are covered: biological networks; automated construction of three-dimensional cell models using experimental data; modeling of protein complexes; prediction of non-specific and transient protein interactions; thermodynamic and kinetic effects of crowding; cellular membrane modeling; and modeling of chromosomes. The review presents an expert opinion on the current state-of-the-art in these various aspects of structural modeling in cellular biology, and the prospects of future developments in this emerging field.