engleski

Prediction of initiation sites for protein folding with alpha-helix preferences

Background and purpose: The formation of alpha- helices is thought to direct folding in helical and partly helical proteins. Particularly stable helices may be able to retain information about early folding events. Our goal was to test this hypothesis and to develop fast software package for prediction of helix nucleation and folding initiation sites in protein sequence. Methods: A statistical procedure used in this work consists in evaluating folding initiation parameter for each residue in tested sequence by using middle- helix preference functions and geometric average of position specific middle-helix preferences. The best known crystallographic structures of soluble proteins served for the extraction of preference functions. Position specific frequencies of folding initiation sites in observed helices were collected from proteins with known sequence locations of initiation sites. Results and conclusions: The highest frequency of folding initiation sites is in the middle-helix to C-terminus region of experimentally determined helices. Therefore, initiation sites for protein folding are likely to serve as helix-start signals. Overall sequence maximum of our folding initiation parameter is found at the sequence position which belongs to known folding initiation site and to observed alpha-helix in 84% and 95% of tested sequences respectively. Sequence maximum of this parameter is inside transmembrane helix span for 68% of integral membrane protein sequences of known structure. We developed the Web sever for fast prediction of possible helix nucleation and folding initiation sites at the address: http://pref.etfos.hr/helix-start.

prediction, folding initiation, helix nucleation, helix preference, preference functions

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