Protein loop modeling by using fragment assembly and analytical loop closure

被引:77
作者
Lee, Julian [1 ,2 ]
Lee, Dongseon [3 ]
Park, Hahnbeom [3 ]
Coutsias, Evangelos A. [4 ]
Seok, Chaok [3 ]
机构
[1] Soongsil Univ, Dept Bioinformat & Life Sci, Seoul 156743, South Korea
[2] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA
[3] Seoul Natl Univ, Dept Chem, Seoul 151747, South Korea
[4] Univ New Mexico, Dept Math & Stat, Albuquerque, NM 87131 USA
关键词
loop modeling; protein structure prediction; fragment assembly method; analytical loop closure; loop ensemble; DEPENDENT ROTAMER LIBRARY; HYBRID ENERGY FUNCTION; STRUCTURE PREDICTION; SECONDARY STRUCTURE; MONTE-CARLO; ALGORITHM; SELECTION; PROLINE; SPACE;
D O I
10.1002/prot.22849
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Protein loops are often involved in important biological functions such as molecular recognition, signal transduction, or enzymatic action. The three dimensional structures of loops can provide essential information for understanding molecular mechanisms behind protein functions. In this article, we develop a novel method for protein loop modeling, where the loop conformations are generated by fragment assembly and analytical loop closure. The fragment assembly method reduces the conformational space drastically, and the analytical loop closure method finds the geometrically consistent loop conformations efficiently. We also derive an analytic formula for the gradient of any analytical function of dihedral angles in the space of closed loops. The gradient can be used to optimize various restraints derived from experiments or databases, for example restraints for preferential interactions between specific residues or for preferred backbone angles. We demonstrate that the current loop modeling method outperforms previous methods that employ residue-based torsion angle maps or different loop closure strategies when tested on two sets of loop targets of lengths ranging from 4 to 12.
引用
收藏
页码:3428 / 3436
页数:9
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