Mining viral protease data to extract cleavage knowledge.
BACKGROUND
The motivation is to identify, through machine learning techniques, specific patterns in HIV and HCV viral polyprotein amino acid residues where viral protease cleaves the polyprotein as it leaves the ribosome. An understanding of viral protease specificity may help the development of future anti-viral drugs involving protease inhibitors by identifying specific features of protease activity for further experimental investigation. While viral sequence information is growing at a fast rate, there is still comparatively little understanding of how viral polyproteins are cut into their functional unit lengths. The aim of the work reported here is to investigate whether it is possible to generalise from known cleavage sites to unknown cleavage sites for two specific viruses-HIV and HCV. An understanding of proteolytic activity for specific viruses will contribute to our understanding of viral protease function in general, thereby leading to a greater understanding of protease families and their substrate characteristics.


RESULTS
Our results show that artificial neural networks and symbolic learning techniques (See5) capture some fundamental and new substrate attributes, but neural networks outperform their symbolic counterpart.
Narayanan
Ajit
A
School of Engineering and Computer Sciences (Bioinformatics Laboratory), Old Library, University of Exeter, Exeter EX4 4PT, UK. a.narayanan@ex.ac.uk
Wu
Xikun
X
Yang
Z Rong
ZR
D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D001185:Artificial Intelligence; D030562:Databases, Protein; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D004795:Enzyme Stability; D006678:HIV / Q000201:enzymology*; D016174:Hepacivirus / Q000201:enzymology*; D016247:Information Storage and Retrieval / Q000379:methods*; D008969:Molecular Sequence Data; D009415:Nerve Net; D011485:Protein Binding; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
D000596:Amino Acids; D014764:Viral Proteins; D010450:Endopeptidases