A new sequence representation as applied in better specificity elucidation for human immunodeficiency virus type 1 protease

Factor analysis scales of generalized amino acid information (FASGAI) involving hydrophobicity, alpha and turn propensities, bulky properties, compositional characteristics, local flexibility, and electronic properties were derived from 516 property parameters of 20-coded amino acids, and was then employed to represent sequence structures of 746 peptides with 8 amino acid residues. Cleavage site prediction models for human immunodeficiency virus type 1 protease by linear discriminant analysis and support vector machine with radial basis function kernel were constructed to identify if they could be cleaved or not, and were further utilized to investigate the cleavage specificity. These diversified properties, including the bulky properties, secondary conformation characteristics, electronic properties, and hydrophobicity at the first, the second, the fourth, the fifth, and the sixth residue, are possibly important factors in determining HIV PR cleavage or not. Particularly, maximal positive and negative influences result from the bulky properties of different sites. Further results from analysis of variance also likely reflect that the HIV PR recognizes diversified key properties of various sites in the octameric sequences. Satisfactory results show that FASGAI can not only be used to represent sequence structures of various functional peptides, but alsoprovide a potential feasible measure for exploring relationship between protein motif sequences and their functions.