Sundaramurthy Pandurangan, Sreenivasan Raashi, Shameer Khader, Gakkhar Sunita, Sowdhamini Ramanathan
Bioinformation. 2011;7(7):352-9. doi: 10.6026/97320630007352. Epub 2011 Dec 10.
Understanding the functional and structural implication of a protein encoded in novel genes using function association or fold recognition approaches remains to be a challenging task in the current era of genomes, metagenomes and personal genomes. In an attempt to enhance potential-based fold-recognition methods in recognizing remote homology between proteins, we propose a new approach "Higher Order Residue Interaction Based ALgorithm for Fold REcognition (HORIBALFRE)". Higher order residue interactions refer to a class of interactions in protein structures mediated by C(α) or C(β) atoms within a pre-defined distance cut-off. Higher order residue interactions (pairwise, triplet and quadruplet interactions) play a vital role in attaining the stable conformation of a protein structure. In HORIBALFRE, we incorporated the potential contributions from two body (pairwise) interactions, three body (triplet interactions) and four-body (quadruple interaction) interactions, to implement a new fold recognition algorithm. Core of HORIBALFRE algorithm includes the potentials generated from a library of protein structure derived from manually curated CAMPASS database of structure based sequence alignment. We used Fischer's dataset, with 68 templates and 56 target sequences, derived from SCOP database and performed one-against-all sequence alignment using TCoffee. Various potentials were derived using custom scripts and these potentials were incorporated in the HORIBALFRE algorithm. In this manuscript, we report outline of a novel fold recognition algorithm and initial results. Our results show that inclusion of quadruplet class of higher order residue interaction improves fold recognition.
在当今基因组、宏基因组和个人基因组时代，利用功能关联或折叠识别方法来理解新基因中编码蛋白质的功能和结构含义仍然是一项具有挑战性的任务。为了增强基于势能的折叠识别方法在识别蛋白质间远程同源性方面的能力，我们提出了一种新方法“基于高阶残基相互作用的折叠识别算法（HORIBALFRE）”。高阶残基相互作用是指在蛋白质结构中由预定义距离截止范围内的C(α)或C(β)原子介导的一类相互作用。高阶残基相互作用（成对、三联体和四联体相互作用）在实现蛋白质结构的稳定构象中起着至关重要的作用。在HORIBALFRE中，我们纳入了两体（成对）相互作用、三体（三联体相互作用）和四体（四联体相互作用）的潜在贡献，以实现一种新的折叠识别算法。HORIBALFRE算法的核心包括从基于结构的序列比对的人工整理的CAMPASS数据库衍生的蛋白质结构库中生成的势能。我们使用了来自SCOP数据库的Fischer数据集，其中有68个模板和56个目标序列，并使用TCoffee进行了一对所有的序列比对。使用自定义脚本得出了各种势能，并将这些势能纳入HORIBALFRE算法中。在本论文中，我们报告了一种新型折叠识别算法的概述和初步结果。我们的结果表明，纳入四联体类的高阶残基相互作用可提高折叠识别能力。
