ProSup: a refined tool for protein structure alignment

Peter Lackner, Walter A. Koppensteiner, Manfred J. Sippl, Francisco S. Domingues
2000 Protein Engineering Design & Selection  
several solutions with comparable extent of similarity can be observed. They can differ in small shifts in secondary structure Manfred J.Sippl 1,3 and Francisco S.Domingues 1 elements, e.g. a shift of two residues in β-strands, but also 1 Center for Applied Molecular Engineering, Institute for Chemistry and correspond to alignments of different regions, e.g. different Biochemistry, University of Salzburg, Jakob-Haringer Str. 3, A-5020 domains. Therefore, alternative solutions are relevant
more » ... are relevant whenever Salzburg and 3 ProCeryon Biosciences GmbH, Jakob-Haringer Str. 3, A-5020 an alignment is needed, as in the evaluation of structure Salzburg, Austria prediction (Lackner et al., 1999). Here we investigated and 2 To whom correspondence should be addressed optimized the ProSup structure comparison program (Feng We investigated and optimized a method for structure and Sippl, 1996) . In ProSup the r.m.s.d. is kept below a comparison which is based on rigid body superimposition. threshold by defining a certain distance cutoff for equivalent The method maximizes the number of structurally equivaresidues. This cutoff applies during both major steps of the lent residues while keeping the root mean square deviation algorithm, (1) the iterative expansion of preliminary alignments constant. The resulting number of equivalent residues then and (2) the dynamic programming-based refinement. Pairs of provides an adequate similarity measure, which is easy to small fragments having an r.m.s.d. below a certain cutoff are interpret. We demonstrate that the approach is able to selected for initial superimpositions. This in general results in detect remote structural similarity. We show that the a number of distinct alignments. ProSup provides different number of equivalent residues is a suitable measure for filters applicable to the alignments, in order to remove regions ranking database searches and that the results are in of non-significant similarity. good agreement with expert knowledge protein structure We describe and discuss the ProSup algorithm and its classification. Structure comparison frequently has multiple parameters in detail in the Materials and methods section. In solutions. The approach that we use provides a range of the Results and discussion section we (1) show that ProSup is alternative alignments rather a single solution. We discuss able to detect remote structural similarity using a test set of the nature of alternative solutions on several examples. 10 protein pairs reported in the literature, (2) compare the Keywords: alternative alignments/structure similarity measure/ ranking of ProSup with the ranking of DALI (Holm and superimposition Sander, 1993) , which is based on the alignment of distance matrices, (3) compare the ProSup ranking with the expert knowledge-derived structure classification of SCOP (Murzin et al., 1995), (4) calculate a measure of statistical significance for the structure alignments, (5) discuss the problem of side
doi:10.1093/protein/13.11.745 pmid:11161105 fatcat:ggsyr43o4raldb4hp3ghbri64u