Savol Andrej J, Chennubhotla Chakra S
Dept. of Computational and Systems Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States ; Joint Carnegie Mellon University-University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, Pennsylvania 15260, United States.
Dept. of Computational and Systems Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
J Chem Theory Comput. 2014 Aug 12;10(8):2964-2974. doi: 10.1021/ct500361w. Epub 2014 Jun 13.
Experiments and atomistic simulations of polypeptides have revealed structural intermediates that promote or inhibit conformational transitions to the native state during folding. We invoke a concept of "kinetic frustration" to quantify the prevalence and impact of these behaviors on folding rates within a large set of atomistic simulation data for 10 fast-folding proteins, where each protein's conformational space is represented as a Markov state model of conformational transitions. Our graph theoretic approach addresses what conformational features correlate with folding inhibition and therefore permits comparison among features within a single protein network and also more generally between proteins. Nonnative contacts and nonnative secondary structure formation can thus be quantitatively implicated in inhibiting folding for several of the tested peptides.
对多肽的实验和原子模拟揭示了一些结构中间体，它们在折叠过程中促进或抑制向天然状态的构象转变。我们引入“动力学受挫”的概念，以量化这些行为在10种快速折叠蛋白质的大量原子模拟数据中对折叠速率的普遍性和影响，其中每种蛋白质的构象空间表示为构象转变的马尔可夫状态模型。我们的图论方法解决了哪些构象特征与折叠抑制相关的问题，因此允许在单个蛋白质网络内的特征之间进行比较，并且更广泛地在蛋白质之间进行比较。因此，对于几种测试肽，非天然接触和非天然二级结构的形成可以定量地与抑制折叠相关联。
