Salem Saeed, Zaki Mohammed J, Bystroff Chris
Department of Computer Science, North Dakota State University, Fargo, ND 58108, USA.
Algorithms Mol Biol. 2010 Jan 4;5:12. doi: 10.1186/1748-7188-5-12.
Proteins have evolved subject to energetic selection pressure for stability and flexibility. Structural similarity between proteins that have gone through conformational changes can be captured effectively if flexibility is considered. Topologically unrelated proteins that preserve secondary structure packing interactions can be detected if both flexibility and Sequential permutations are considered. We propose the FlexSnap algorithm for flexible non-topological protein structural alignment.
The effectiveness of FlexSnap is demonstrated by measuring the agreement of its alignments with manually curated non-sequential structural alignments. FlexSnap showed competitive results against state-of-the-art algorithms, like DALI, SARF2, MultiProt, FlexProt, and FATCAT. Moreover on the DynDom dataset, FlexSnap reported longer alignments with smaller rmsd.
We have introduced FlexSnap, a greedy chaining algorithm that reports both sequential and non-sequential alignments and allows twists (hinges). We assessed the quality of the FlexSnap alignments by measuring its agreements with manually curated non-sequential alignments. On the FlexProt dataset, FlexSnap was competitive to state-of-the-art flexible alignment methods. Moreover, we demonstrated the benefits of introducing hinges by showing significant improvements in the alignments reported by FlexSnap for the structure pairs for which rigid alignment methods reported alignments with either low coverage or large rmsd.
An implementation of the FlexSnap algorithm will be made available online at http://www.cs.rpi.edu/~zaki/software/flexsnap.
蛋白质在稳定性和灵活性方面经历了能量选择压力而不断进化。如果考虑灵活性，那么经历构象变化的蛋白质之间的结构相似性就能被有效捕捉。如果同时考虑灵活性和序列排列，那么就能检测到保留二级结构堆积相互作用的拓扑无关蛋白质。我们提出了用于灵活非拓扑蛋白质结构比对的FlexSnap算法。
通过测量其比对结果与人工整理的非序列结构比对结果的一致性，证明了FlexSnap的有效性。FlexSnap与DALI、SARF2、MultiProt、FlexProt和FATCAT等现有算法相比，取得了具有竞争力的结果。此外，在DynDom数据集上，FlexSnap报告的比对结果具有更长的长度和更小的均方根偏差。
我们引入了FlexSnap，这是一种贪心链接算法，它既能报告序列比对结果，也能报告非序列比对结果，并且允许扭转（铰链）。我们通过测量其与人工整理的非序列比对结果的一致性来评估FlexSnap比对结果的质量。在FlexProt数据集上，FlexSnap与现有最先进的灵活比对方法相比具有竞争力。此外，对于刚性比对方法报告的覆盖度低或均方根偏差大的结构对，我们通过展示FlexSnap报告的比对结果有显著改进，证明了引入铰链的好处。
FlexSnap算法的实现将在http://www.cs.rpi.edu/~zaki/software/flexsnap上在线提供。
