A hierarchical approach to protein molecular evolution
A hierarchical approach to protein molecular evolution
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DOI：
10.1073/pnas.96.6.2591
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发表时间：
1999-03-16
影响因子：
11.1
通讯作者：
Deem, MW
中科院分区：
文献类型：
--
作者：
Bogarad, LD;Deem, MW
尽管蛋白质序列空间基本上是无限复杂的，但生物多样性已经进化。我们提出了一个分层的方法来有效地搜索这个空间，并量化我们的方法与蒙特卡洛模拟的进化潜力。这些模拟表明，编码结构的非同源并列是新的三级蛋白质折叠生产的限速步骤。低能二级结构的非同源“交换”使模拟蛋白质的结合常数相对于单独的碱基取代增加了约10（7）。我们的方法的应用包括nem蛋白质折叠的产生和疾病的分子进化建模。
Biological diversity has evolved despite the essentially infinite complexity of protein sequence space. We present a hierarchical approach to the efficient searching of this space and quantify the evolutionary potential of our approach with Monte Carlo simulations. These simulations demonstrate that nonhomologous juxtaposition of encoded structure is the rate-limiting step in the production of new tertiary protein folds. Nonhomologous "swapping" of low-energy secondary structures increased the binding constant of a simulated protein by approximate to 10(7) relative to base substitution alone. Applications of our approach include the generation of nem protein folds and modeling the molecular evolution,of disease.