Protein folding: From the Levinthal paradox to structure prediction
Protein folding: From the Levinthal paradox to structure prediction
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DOI：
10.1006/jmbi.1999.3006
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发表时间：
1999-10-22
影响因子：
5.6
通讯作者：
Honig, B
中科院分区：
文献类型：
--
作者：
Honig, B
本文是对近40年来蛋白质折叠领域发展的个人看法。除了它的历史方面，文章提出了蛋白质折叠原理的观点，特别强调这些原理与蛋白质结构预测问题的关系。有人认为，尽管有很多新的东西，但我们目前对蛋白质折叠的理解的基本要素在许多年前就被研究人员预测到了。这些要素包括认识到多肽主链作为蛋白质构象、分层蛋白质折叠和多种折叠途径的决定因素的核心重要性。重要的进展领域包括对许多蛋白质折叠途径的详细描述，以及对决定蛋白质稳定性的物理化学力的基本理解。尽管有了这些发展，折叠预测算法在识别给定序列的正确折叠时仍然遇到困难。这可能是由于许多蛋白质的至少几个交替构象之间的自由能差不大的可能性。蛋白质结构预测的重大进展主要是由于序列和结构数据库的爆炸性增长。然而，进一步的进展可能部分取决于将数据库中的信息与蛋白质折叠的物理化学研究得出的原理和算法结合起来的能力。本文概述了一种整合这两个领域的方法，具体参照PrISM程序，该程序是一个完全集成的序列（结构分析/折叠识别/同源模型构建软件系统）。(C) 1999学术出版社。
This article is a personal perspective on the developments in the field of protein folding over approximately the last 40 years. In addition to its historical aspects, the article presents a view of the principles of protein folding with particular emphasis on the relationship of these principles to the problem of protein structure prediction. It is argued that despite much that is new, the essential elements of our current understanding of protein folding were anticipated by researchers many years ago. These elements include the recognition of the central importance of the polypeptide backbone as a determinant of protein conformation, hierarchical protein folding, and multiple folding pathways. Important areas of progress include a detailed characterization of the folding pathways of a number of proteins and a fundamental understanding of the physical chemical forces that determine protein stability. Despite these developments, fold prediction algorithms still encounter difficulties in identifying the correct fold for a given sequence. This may be due to the possibility that the free energy differences between at least a few alternate conformations of many proteins are-not large. Significant progress in protein structure prediction has been due primarily to the explosive growth of sequence and structural databases. However, further progress is Likely to depend in part on the ability to combine information available from databases with principles and algorithms derived from physical chemical studies of protein folding. An approach to the integration of the two areas is outlined with specific reference to the PrISM program that is a fully integrated sequence( structural-analysis/fold-recognition/homology model building software system. (C) 1999 Academic Press.