De novo backbone scaffolds for protein design
De novo backbone scaffolds for protein design
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DOI：
10.1002/prot.22651
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发表时间：
2010-04-01
影响因子：
2.9
通讯作者：
Taylor, William R.
中科院分区：
文献类型：
--
作者：
MacDonald, Jarnes T.;Maksimiak, Katarzyna;Taylor, William R.
近年来，在计算蛋白质设计领域取得了重大进展，包括基于实验解决结构的骨架骨架的酶的成功计算设计。随着在更复杂的系统上取得进一步进展，很可能需要对蛋白质骨架构象进行大规模取样。消除必须使用基于已知蛋白质骨架的支架的限制是解决该问题的潜在方法。考虑到这一应用程序，我们描述了一种方法，系统地构建了大量的从头骨架结构的理想化拓扑形式在自上而下的分层方法。分析了这些新型骨架支架的结构特性，并与蛋白质数据库（PDB）中的一组高分辨率实验结构进行了比较。结果发现，拉马钱德兰图分布和相对γ-和β-转频率是类似的PDB中发现的。用RosettaDesign对从头构建的支架进行序列设计，能量分布和氨基酸组成与重新设计的实验解决的骨架的结果相当。
In recent years, there have been significant advances in the field of computational protein design including the successful computational design of enzymes based on backbone scaffolds from experimentally solved structures. it is likely that large-scale sampling of protein backbone conformations will become necessary as further progress is made on more complicated systems. Removing the constraint of having to use scaffolds based on known protein backbones is a potential method of solving the problem. With this application in mind, we describe a method to systematically construct a large number of de novo backbone structures from idealized topological forms in a top-down hierarchical approach. The structural properties of these novel backbone scaffolds were analyzed and compared with a set of high-resolution experimental structures from the protein data bank (PDB). It was found that the Ramachandran plot distribution and relative gamma- and beta-turn frequencies were similar to those found in the PDB. The de novo scaffolds were sequence designed with RosettaDesign, and the energy distributions and amino acid compositions were comparable with the results for redesigned experimentally solved backbones.