Fr-TM-align: a new protein structural alignment method based on fragment alignments and the TM-score

• Published in: BMC bioinformatics Vol. 9; no. 1; p. 531
• Main Authors: Pandit, Shashi Bhushan, Skolnick, Jeffrey
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.12.2008; BioMed Central; BMC
• Subjects: Algorithms; Animals; Computational biology; Computational Biology - methods; Computers; Databases, Protein; Humans; Methodology; Models, Statistical; Molecular Sequence Data; Protein Conformation; Protein Structure, Tertiary; Proteins; Proteins - chemistry; Sequence Alignment - methods; Sequence Analysis, Protein - methods; Software; Structure; United States
• ISSN: 1471-2105; 1471-2105
• DOI: 10.1186/1471-2105-9-531

Protein tertiary structure comparisons are employed in various fields of contemporary structural biology. Most structure comparison methods involve generation of an initial seed alignment, which is extended and/or refined to provide the best structural superposition between a pair of protein structures as assessed by a structure comparison metric. One such metric, the TM-score, was recently introduced to provide a combined structure quality measure of the coordinate root mean square deviation between a pair of structures and coverage. Using the TM-score, the TM-align structure alignment algorithm was developed that was often found to have better accuracy and coverage than the most commonly used structural alignment programs; however, there were a number of situations when this was not true. To further improve structure alignment quality, the Fr-TM-align algorithm has been developed where aligned fragment pairs are used to generate the initial seed alignments that are then refined using dynamic programming to maximize the TM-score. For the assessment of the structural alignment quality from Fr-TM-align in comparison to other programs such as CE and TM-align, we examined various alignment quality assessment scores such as PSI and TM-score. The assessment showed that the structural alignment quality from Fr-TM-align is better in comparison to both CE and TM-align. On average, the structural alignments generated using Fr-TM-align have a higher TM-score (~9%) and coverage (~7%) in comparison to those generated by TM-align. Fr-TM-align uses an exhaustive procedure to generate initial seed alignments. Hence, the algorithm is computationally more expensive than TM-align. Fr-TM-align, a new algorithm that employs fragment alignment and assembly provides better structural alignments in comparison to TM-align. The source code and executables of Fr-TM-align are freely downloadable at: http://cssb.biology.gatech.edu/skolnick/files/FrTMalign/.