Improving the prediction of secondary structure of –TIM-barrel— enzymes

The information contained in aligned sets of homologous protein sequences should improve the score of secondary structure prediction. Seven different enzymes having the (β/α)8 or TIM-barrel fold were used to optimize the prediction with regard to this class of enzymes. The α-helix, β-strand and loop propensities of the Garnier—Osguthorpe—Robson method were averaged at aligned residue positions, leading to a significant improvement over the average score obtained from single sequences. The increased accuracy correlates with the average sequence variability of the aligned set. Further improvements were obtained by using the following averaged properties as weights for the averaged state propensities: amphipathic moment and α-helix; hydropathy and β-strand; chain flexibility and loop. The clustering of conserved residues at the C-terminal ends of the 13-strands was used as an additional positive weight for β-strand propensity and increased the prediction of otherwise unpredicted β-strands decisively. The automatic weighted prediction method identifies >95% of the secondary structure elements of the set of seven TIM-barrel enzymes.