NON-HOMOLOGY KNOWLEDGE-BASED PREDICTION OF THE PAPAIN PROSEGMENT FOLDING PATTERN - A DESCRIPTION OF PLAUSIBLE FOLDING AND ACTIVATION MECHANISMS

Background: A detailed knowledge of three-dimensional conformations is necessary in order to understand the close relationship between prote in structure and function. Among current methodologies, homology model ing is an important tool for obtaining reliable geometries and it prov ides a direct alternative to X-ray or NMR techniques. In contrast, pre dictive methods with no three-dimensional template (non-homology) stil l require further Validation and systematization. Results: Here, we pr esent a non-homology knowledge-based strategy for the structural predi ction of the proregion of a cysteine proteinase zymogen. This method a nalyzes individual sequences and multiple alignments of homologous seq uences, making use of different published algorithms and incorporating all available structure-related information to obtain improved predic tions. Our strategy yielded acceptable secondary structure and general three-dimensional assignments when compared with crystallographic dat a from homologous proteins. Conclusions: We discuss our successes and failures as a contribution to non-homology prediction development. In addition, based on the information analyzed and generated in this work , we propose plausible folding and activation mechanisms for thiol-pro teinase precursors that attempt to shed tight on the molecular basis o f prosegment functions.