Multiscale modeling of proteins.
Multiscale modeling of proteins.
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DOI：
10.1021/ar9001476
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发表时间：
2010-02
影响因子：
18.3
通讯作者：
V. Tozzini
中科院分区：
文献类型：
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作者：
V. Tozzini
活细胞内的活动基于生物分子之间相互作用的复杂网络，通过生化过程交换信息和能量。这些事件发生在不同的尺度上，从纳米尺度到宏观尺度，在空间域中跨越约10个数量级，在时间域中跨越约15个数量级。因此，通常使用许多不同的建模技术，每种技术都适用于特定的时间或空间尺度。此外，一个单一的过程往往跨越一个以上的时间或空间尺度。因此，有必要在多尺度方法中结合建模技术。在这个帐户中，我首先回顾了生物系统的不同建模方法，从量子力学到粗粒度和连续性描述，通过原子力场模拟。特别注意的是，他们的组合在不同的可能的多尺度方法和相关的问题和问题，他们在空间和时间域的相干匹配。这些方面通常被认为是次要的，但事实上，当目标是连贯和完整地描述生物过程时，它们具有主要的相关性。随后，通过两个典型的例子来说明应用：（i）绿色荧光蛋白（GFP）家族和（ii）参与人类免疫缺陷病毒（HIV）复制周期的蛋白质。GFP是目前用于监测活细胞内蛋白质运输的最常用标记之一;纳米生物技术和细胞生物学强烈依赖于它们在荧光显微镜技术中的使用。详细了解艾滋病毒病毒特异性酶（特别是艾滋病毒蛋白酶和整合酶）的作用对于研究针对这种疾病的新型治疗策略是必要的。因此，多年来深入研究所积累的深刻见解是本账户的一个极好框架。这两个生物分子系统的最重要的相关性最近被2008年的两个诺贝尔奖的分配所证实：在化学中发现GFP和在医学中发现HIV。因此，这些蛋白质研究基本上所有可用的建模技术，使他们成为理想的例子，研究蛋白质建模的多尺度方法的细节。
The activity within a living cell is based on a complex network of interactions among biomolecules, exchanging information and energy through biochemical processes. These events occur on different scales, from the nano- to the macroscale, spanning about 10 orders of magnitude in the space domain and 15 orders of magnitude in the time domain. Consequently, many different modeling techniques, each proper for a particular time or space scale, are commonly used. In addition, a single process often spans more than a single time or space scale. Thus, the necessity arises for combining the modeling techniques in multiscale approaches. In this Account, I first review the different modeling methods for bio-systems, from quantum mechanics to the coarse-grained and continuum-like descriptions, passing through the atomistic force field simulations. Special attention is devoted to their combination in different possible multiscale approaches and to the questions and problems related to their coherent matching in the space and time domains. These aspects are often considered secondary, but in fact, they have primary relevance when the aim is the coherent and complete description of bioprocesses. Subsequently, applications are illustrated by means of two paradigmatic examples: (i) the green fluorescent protein (GFP) family and (ii) the proteins involved in the human immunodeficiency virus (HIV) replication cycle. The GFPs are currently one of the most frequently used markers for monitoring protein trafficking within living cells; nanobiotechnology and cell biology strongly rely on their use in fluorescence microscopy techniques. A detailed knowledge of the actions of the virus-specific enzymes of HIV (specifically HIV protease and integrase) is necessary to study novel therapeutic strategies against this disease. Thus, the insight accumulated over years of intense study is an excellent framework for this Account. The foremost relevance of these two biomolecular systems was recently confirmed by the assignment of two of the Nobel prizes in 2008: in chemistry for the discovery of GFP and in medicine for the discovery of HIV. Accordingly, these proteins were studied with essentially all of the available modeling techniques, making them ideal examples for studying the details of multiscale approaches in protein modeling.