FlexSnap: Flexible Non-sequential Protein Structure 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 webcite.The wide spectrum of functions performed by proteins are enabled by their intrinsic flexibility [1]. It is known that proteins go through conformational changes to perform their functions. Homologous proteins have evolved to adopt conformational changes in their structure. Therefore, similarity between two proteins which have similar structures with one of them having undergone a conformational change will not be captured unless flexibility is considered.The problem of flexible protein structural alignment has not received much attention. Even though there are a plethora of methods for protein structure comparison [2-8], the majority of the existing methods report only sequential alignments and thus cannot capture non-sequential alignments. Non-sequential similarity can occur naturally due to circular permutations [9] or convergent evolution [10]. The case is even harder f