Backbone dependency further improves side chain prediction efficiency in the Energy-based Conformer Library (bEBL).
Backbone dependency further improves side chain prediction efficiency in the Energy-based Conformer Library (bEBL).
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DOI：
10.1002/prot.24685
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发表时间：
2014-11
影响因子：
2.9
通讯作者：
Senes, Alessandro
中科院分区：
文献类型：
--
作者：
Subramaniam, Sabareesh;Senes, Alessandro
侧链优化是许多蛋白质建模应用程序的一个组成部分。在这些应用中，侧链的构象自由度通常使用离散的、频繁出现的构象的文库来探索。因为侧链优化可以引起计算密集型组合问题，所以这些构象文库的性质对于确保侧链预测的效率和准确性是重要的。我们以前开发了一种创新的方法来创建具有增强性能的构象异构体库。基于能量的蛋白质库（EBL）是从晶体结构出发，通过分析构象异构体与大量天然蛋白质环境之间的能量相互作用而建立的。该过程指导选择具有最高倾向的构象异构体，以适应应容纳侧链的空间。由于该方法需要大量的晶体学数据集，因此以主链独立的方式创建EBL。然而，众所周知，侧链构象强烈依赖于局部骨架几何形状，并且骨架依赖性文库在侧链优化中更有效。在这里，我们提出了一个骨干依赖版本的EBL，bEBL，其构象独立排序的每个人口区域的Ramachandran空间。所得到的文库密切反映了侧链构象的局部骨架依赖性分布。与EBL相比，我们证明了bEBL使用更少的构象异构体来产生类似的侧链预测结果，从而进一步提高了相对于已经高效的骨架独立版本的文库的性能。
Side chain optimization is an integral component of many protein modeling applications. In these applications, the conformational freedom of the side chains is often explored using libraries of discrete, frequently occurring conformations. Because side chain optimization can pose a computationally intensive combinatorial problem, the nature of these conformer libraries is important for ensuring efficiency and accuracy in side chain prediction. We have previously developed an innovative method to create a conformer library with enhanced performance. The Energy-Based Library (EBL) was obtained by analyzing the energetic interactions between conformers and a large number of natural protein environments from crystal structures. This process guided the selection of conformers with the highest propensity to fit into spaces that should accommodate a side chain. Because the method requires a large crystallographic data-set, the EBL was created in a backbone-independent fashion. However, it is well established that side chain conformation is strongly dependent on the local backbone geometry, and that backbone-dependent libraries are more efficient in side chain optimization. Here we present a backbone-dependent version of the EBL, the bEBL, whose conformers are independently sorted for each populated region of Ramachandran space. The resulting library closely mirrors the local backbone-dependent distribution of side chain conformation. Compared to the EBL, we demonstrate that the bEBL uses fewer conformers to produce similar side chain prediction outcomes, thus further improving performance with respect to the already efficient backbone-independent version of the library.
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影响因子：
2.9
作者：
Krivov, Georgii G.;Shapovalov, Maxim V.;Dunbrack, Roland L., Jr.
通讯作者：
Dunbrack, Roland L., Jr.
DOI：
10.1016/s0969-2126(99)80176-2
发表时间：
1999-09-15
期刊：
STRUCTURE WITH FOLDING & DESIGN
影响因子：
--
作者：
Gordon, DB;Mayo, SL
通讯作者：
Mayo, SL
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
14.9
作者：
Kim, DE;Chivian, D;Baker, D
通讯作者：
Baker, D
DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Chen VB;Arendall WB 3rd;Headd JJ;Keedy DA;Immormino RM;Kapral GJ;Murray LW;Richardson JS;Richardson DC
通讯作者：
Richardson DC