Analysis of the code relating sequence to conformation in globular proteins. An informational analysis of the role of the residue in determining the conformation of its neighbours in the primary sequence

摘要

p1. The effect exerted by a residue on the conformation of neighbouring residues was analysed by using data from nine globular proteins of known sequence and conformation. 2. An information measure was used which estimated the role of a residue in influencing neighbouring conformations and also its tendency to influence the lengths of runs of residues in that conformation. This measure was estimated for each residue in all conformations defined by domains on the ?, ψ diagram. 3. Plots of the information measure yielded an intercept, which was a measure of intra-residue information for a residue. The slope was a measure of the statistical co-operativity or tendency of the residue to influence the occurrence of its neighbours in runs of a particular conformation. Both parameters are a function of the residue type. Statistical co-operativity is found in the αsub1/sub-helical (Hsub1/sub) and β-pleated-sheet (Psub2/sub) conformations and, to a lesser extent, in their distorted variants Hsub2/sub and Psub1/sub. 4. The directional nature of these influences for Hsub1/sub and Psub2/sub conformations is illustrated by plots of the information measure against the distance im/i from the residue, for im/i=?10 to +10. 5. The results for statistical co-operativity are discussed in relation to theories of helix–coil and pleated-sheet–coil transitions. The value of the information-theory-derived parameters in obtaining is/i parameters for the Zimm & Bragg (1959) equations is illustrated. 6. Directional effects are discussed with particular relation to mechanisms of the termination of helices and the involvement of the αsubII/sub conformation and also to discontinuities in pleated-sheet conformations./p