Energetics of multihelix interactions in protein folding: Application to myoglobin

• Published in: Biopolymers
• Main Authors: Gerritsen, Mirjam, Chou, Kuo‐Chen, Némethy, George, Scheraga, Harold A.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 1985
• Subjects: Sperm whale
• Online Access: http://dx.doi.org/10.1002/bip.360240714; http://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fbip.360240714; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fbip.360240714; https://onlinelibrary.wiley.com/doi/pdf/10.1002/bip.360240714

Abstract Conformational‐energy calculations have been carried out in order to determine favorable packing arrangements within a group of α‐helices. The influence of side chains and of the number of interacting α‐helices on the mode of packing was analyzed. In this work, our earlier methods for computing the packing energy of a pair of α‐helices [Chou, K.‐C., Némethy, G. & Scheraga, H. A. (1984) J. Am. Chem. Soc. 106 , 3161–3170] have been extended to treat the interactions among several helices. Also, new algorithms allow the matching of standard peptide geometry to x‐ray coordinates of helical complexes and the analysis of interrelations between several helices. As a specific test case, the packing of three neighboring α‐helices, viz., the A, G, and H helices of sperm whale myoglobin, was considered. Minimum‐energy arrangements were computed for the separate A‐H and the G‐H α‐helix pairs as well as for the A‐G‐H three‐helix complex. For the packing of the nearly antiparallel G and H α‐helices, the same optimal structure was obtained in two‐ and three‐helix complexes, indicating that a single packing arrangement is specifically favored by interhelix interactions. For the pair of nearly perpendicular A and H α‐helices, interactions are less specific, so that there is no unique optimal structure in the two‐helix complex; in the three‐helix complex, however, a specific mode of packing is favored even for the A‐H pair. This result indicates that the presence of other nearby α‐helices can influence the packing of a given α‐helix pair. The computed arrangement of the A‐G‐H complex is very close to that of the crystallographically determined structure. These results can be used to make deductions about the likely sequence of events in protein folding, where, in this particular case, it appears that the G‐H helix pair may form first and then induce proper orientation of the A helix.