engleski

Prediction of protein folding initiation sites with alpha-helix preferences

In view of hierarchical models of folding, protein folds through intermediate states of increasing level of order, starting with native-like secondary structure. If this is the case, then the local interactions are necessary prerequisite for both the formation of native secondary structure and foldability of proteins. In particular the formation of alpha-helices is thought to direct the folding. We analyzed the data from the literature concerning the existence and location of folding intermediates and initiation sites. The results have shown that folding initiation sites assuming helical structure are associated with the middle region of the corresponding native helices. A procedure for detection of folding initiation sites based on the use of middle helix preferences has been developed. The method utilizes preference functions [1], as well as position specific helix preferences, when searching for the segments with pronounced conformational bias towards mid alpha-helix. The tests performed on 100 proteins with the best known 3D structures and on 37 known folding initiation sites revealed that: a) preference-derived parameter is well suited for the detection of middle part of helices and b) strongly predicted middle helical segments correspond to protein folding initiation sites. Therefore, just by setting a high parameter threshold one can weed out helices that are not part of initiation sites. Prediction efficiency of 92% is reached with the threshold set at 3.6. The method is available via automatic server on the WWW site http://pref.etfos.hr/helix-start. [1] D. Juretic et al, J. Chem. Inf. Comput. Sci., 38, (1998) 575

helix initiation

nije evidentirano