Non-sequential protein structure alignment by conformational space annealing and local refinement.

Protein structure alignment is an important tool for studying evolutionary biology and protein modeling. A tool which intensively searches for the globally optimal non-sequential alignments is rarely found. We propose ALIGN-CSA which shows improvement in scores, such as DALI-score, SP-score, SO-score and TM-score over the benchmark set including 286 cases. We performed benchmarking of existing popular alignment scoring functions, where the dependence of the search algorithm was effectively eliminated by using ALIGN-CSA. For the benchmarking, we set the minimum block size to 4 to prevent much fragmented alignments where the biological relevance of small alignment blocks is hard to interpret. With this condition, globally optimal alignments were searched by ALIGN-CSA using the four scoring functions listed above, and TM-score is found to be the most effective in generating alignments with longer match lengths and smaller RMSD values. However, DALI-score is the most effective in generating alignments similar to the manually curated reference alignments, which implies that DALI-score is more biologically relevant score. Due to the high demand on computational resources of ALIGN-CSA, we also propose a relatively fast local refinement method, which can control the minimum block size and whether to allow the reverse alignment. ALIGN-CSA can be used to obtain much improved alignment at the cost of relatively more extensive computation. For faster alignment, we propose a refinement protocol that improves the score of a given alignment obtained by various external tools. All programs are available from http://lee.kias.re.kr

Assessment Of Predictions Submitted For The Casp7 Domain Prediction Category

This paper details the assessment process and evaluation results for the Critical Assessment of Protein Structure Prediction (CASP7) domain prediction category. Domain predictions were assessed using the Normalized Domain Overlap score introduced in CASP6 and the accuracy of prediction of domain break points. The results of the analysis clearly demonstrate that the best methods are able to make consistently reliable predictions when the target has a structural template, although they are less good when the domain break occurs in a region not covered by a template. The conditions of the experiment meant that it was impossible to draw any conclusions about domain prediction for free modeling targets and it was also difficult to draw many distinctions between the best groups. Two thirds of the targets submitted were single domains and hence regarded as easy to predict. Even those targets defined as having multiple domains always had at least one domain with a similar template structure. © 2007 Wiley-Liss, Inc