Improving protein secondary structure prediction with aligned homologous sequences.
Most recent protein secondary structure prediction methods use sequence alignments to improve the prediction quality. We investigate the relationship between the location of secondary structural elements, gaps, and variable residue positions in multiple sequence alignments. We further investigate how these relationships compare with those found in structurally aligned protein families. We show how such associations may be used to improve the quality of prediction of the secondary structure elements, using the Quadratic-Logistic method with profiles. Furthermore, we analyze the extent to which the number of homologous sequences influences the quality of prediction. The analysis of variable residue positions shows that surprisingly, helical regions exhibit greater variability than do coil regions, which are generally thought to be the most common secondary structure elements in loops. However, the correlation between variability and the presence of helices does not significantly improve prediction quality. Gaps are a distinct signal for coil regions. Increasing the coil propensity for those residues occurring in gap regions enhances the overall prediction quality. Prediction accuracy increases initially with the number of homologues, but changes negligibly as the number of homologues exceeds about 14. The alignment quality affects the prediction more than other factors, hence a careful selection and alignment of even a small number of homologues can lead to significant improvements in prediction accuracy.
Di Francesco
V
V
NIH/DCRT/LSB, Bethesda, Maryland 20892-5626, USA. valedf@helix.nih.gov
Garnier
J
J
Munson
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D017433:Protein Structure, Secondary; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid