Towards protein tertiary fold prediction using distance and motif constraints.
Based on a simplified model of the all-alpha class of protein, all packing arrangements of alpha-helices were generated and assessed by both general and specific structural rules. The method was applied to myoglobin and parvalbumin, which were both ranked in the top 4% of folds under the general packing constraints. Incorporation of the restrictions implied by the EF-hand motifs of parvalbumin were sufficient to select the correct fold as one of two (equal scoring) possibilities. Myoglobin scored well under the general packing constraints and the addition of a single distance constraint, implied by haem binding, was sufficient to select the correct fold as one of several candidates. Incorporation of a score for complementary hydrophobic packing between helices further selected myoglobin as a unique fold but did not improve the ranking of parvalbumin. For both proteins, the alpha-helices were predicted from multiply aligned sequences using pattern-matching methods and no specific aspect of the known X-ray structures influenced this or the prediction of the correct folds. Although the method is currently of limited generality, its further applications and extension to a more detailed structural level are discussed.
Taylor
W R
WR
Laboratory of Mathematical Biology, National Institute for Medical Research, Mill Hill, London, UK.
D000595:Amino Acid Sequence; D003461:Crystallography; D008432:Mathematical Computing; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009211:Myoglobin / Q000737:chemistry*; D010320:Parvalbumins / Q000737:chemistry*; D011487:Protein Conformation
D009211:Myoglobin; D010320:Parvalbumins