Energetics of multihelix interactions in protein folding: Application to myoglobin

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.

[1]  L. Pauling,et al.  The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. , 1951, Proceedings of the National Academy of Sciences of the United States of America.

[2]  F. Crick,et al.  The packing of α‐helices: simple coiled‐coils , 1953 .

[3]  M. J. D. Powell,et al.  An efficient method for finding the minimum of a function of several variables without calculating derivatives , 1964, Comput. J..

[4]  I. C. O. B. Nomenclature IUPAC-IUB Commission on Biochemical Nomenclature. Abbreviations and symbols for the description of the conformation of polypeptide chains. Tentative rules (1969). , 1970, Biochemistry.

[5]  H. Scheraga,et al.  Energy parameters in polypeptides. VII. Geometric parameters, partial atomic charges, nonbonded interactions, hydrogen bond interactions, and intrinsic torsional potentials for the naturally occurring amino acids , 1975 .

[6]  H. Scheraga,et al.  Experimental and theoretical aspects of protein folding. , 1975, Advances in protein chemistry.

[7]  R. L. Baldwin Intermediates in protein folding reactions and the mechanism of protein folding. , 1975, Annual review of biochemistry.

[8]  O. Ptitsyn,et al.  A model of myoglobin self-organization. , 1975, Biophysical chemistry.

[9]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1977, Journal of molecular biology.

[10]  V. Lim,et al.  The folding pathway for globins , 1977, FEBS letters.

[11]  C. Chothia,et al.  Structure of proteins: packing of alpha-helices and pleated sheets. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Frederic M. Richards,et al.  Packing of α-helices: Geometrical constraints and contact areas☆ , 1978 .

[13]  A. Efimov Packing of α-helices in globular proteins. Layer-structure of globin hydrophobic cores , 1979 .

[14]  Harold A. Scheraga,et al.  Conformational analysis of proteins: Algorithms and data structures for array processing , 1980 .

[15]  M. Sternberg,et al.  On the prediction of protein structure: The significance of the root-mean-square deviation. , 1980, Journal of molecular biology.

[16]  A. Lesk,et al.  How different amino acid sequences determine similar protein structures: the structure and evolutionary dynamics of the globins. , 1980, Journal of molecular biology.

[17]  C. Chothia,et al.  Helix to helix packing in proteins. , 1981, Journal of molecular biology.

[18]  John E. Dennis,et al.  Algorithm 573: NL2SOL—An Adaptive Nonlinear Least-Squares Algorithm [E4] , 1981, TOMS.

[19]  Harold A. Scheraga,et al.  Influence of interatomic interactions on the structure and stability of polypeptides and proteins , 1981 .

[20]  J. Richardson,et al.  The anatomy and taxonomy of protein structure. , 1981, Advances in protein chemistry.

[21]  H A Scheraga,et al.  Origin of the right-handed twist of beta-sheets of poly(LVal) chains. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[22]  H. Scheraga,et al.  Structure of beta-sheets. Origin of the right-handed twist and of the increased stability of antiparallel over parallel sheets. , 1982, Journal of molecular biology.

[23]  Kuo-Chen Chou,et al.  Energetic approach to the packing of .alpha.-helixes. 1. Equivalent helixes , 1983 .

[24]  G. Némethy Interactions between poly(Gly‐Pro‐Pro) triple helices: A model for molecular packing in collagen , 1983, Biopolymers.

[25]  H. Scheraga,et al.  Energy parameters in polypeptides. 9. Updating of geometrical parameters, nonbonded interactions, and hydrogen bond interactions for the naturally occurring amino acids , 1983 .

[26]  N. A. Kolchanov,et al.  A simple method for the calculation of low energy packings of alpha-helices--a threshold approximation. I. The use of the method to estimate the effects of amino acid substitutions, deletions and insertions in globins. , 1984, Journal of theoretical biology.

[27]  H. Scheraga,et al.  Role of proline …︁ proline interactions in the packing of collagenlike poly(tripeptide) triple helices , 1984, Biopolymers.

[28]  Kuo-Chen Chou,et al.  Energetic approach to the packing of α-helices. II: General treatment of nonequivalent and nonregular helices , 1984 .