Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
Genes (Basel). 2011 Oct 28;2(4):748-62. doi: 10.3390/genes2040748.
Protein sequence, structure, and function are inherently linked through evolution and population genetics. Our knowledge of protein structure comes from solved structures in the Protein Data Bank (PDB), our knowledge of sequence through sequences found in the NCBI sequence databases (http://www.ncbi.nlm.nih.gov/), and our knowledge of function through a limited set of in-vitro biochemical studies. How these intersect through evolution is described in the first part of the review. In the second part, our understanding of a series of questions is addressed. This includes how sequences evolve within structures, how evolutionary processes enable structural transitions, how the folding process can change through evolution and what the fitness impacts of this might be. Moving beyond static structures, the evolution of protein kinetics (including normal modes) is discussed, as is the evolution of conformational ensembles and structurally disordered proteins. This ties back to a question of the role of neostructuralization and how it relates to selection on sequences for functions. The relationship between metastability, the fitness landscape, sequence divergence, and organismal effective population size is explored. Lastly, a brief discussion of modeling the evolution of sequences of ordered and disordered proteins is entertained.
蛋白质的序列、结构和功能通过进化和群体遗传学内在地联系在一起。我们对蛋白质结构的了解来自于蛋白质数据库（PDB）中已解决的结构，对序列的了解来自于 NCBI 序列数据库（http://www.ncbi.nlm.nih.gov/）中发现的序列，对功能的了解则来自于有限的一系列体外生化研究。这三个方面是如何通过进化相互关联的，在综述的第一部分进行了描述。在第二部分中，我们解决了一系列问题。这包括序列在结构内如何进化，进化过程如何使结构转变，折叠过程如何通过进化而改变，以及这可能带来的适应性影响。超越静态结构，讨论了蛋白质动力学（包括正常模式）的进化，以及构象集合和结构无序蛋白质的进化。这与新结构形成的作用以及它与序列选择功能的关系有关。还探讨了亚稳性、适应度景观、序列分歧和生物体有效种群大小之间的关系。最后，简要讨论了有序和无序蛋白质序列进化的建模问题。
