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Packing interactions of aib‐containing helices: Molecular modeling of parallel dimers of simple hydrophobic helices and of alamethicin
Author(s) -
Breed J.,
Kerr I. D.,
Sankararamakrishnan R.,
Sansom M. S. P.
Publication year - 1995
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360350610
Subject(s) - alamethicin , helix (gastropod) , chemistry , crystallography , molecular dynamics , alpha helix , triple helix , stereochemistry , circular dichroism , membrane , computational chemistry , bilayer , biochemistry , ecology , snail , biology
α‐Aminoisobutyric acid (Aib) is a helicogenic α,α‐dimethyl amino acid found in channel‐forming peptaibols such as alamethicin. Possible effects of Aib on helix–helix packing are analyzed. Simulated annealing via restrained molecular dynamics is used to generate ensembles of approximately parallel helix dimers. Analysis of variations in geometrical and energetic parameters within ensembles defines how tightly a pair of helices interact. Simple hydrophobic helix dimers are compared: Ala 20 , Leu 20 , Aib 20 , and P20, the latter a simple channel‐forming peptide [G. Menestrina, K. P. Voges, G, Jung, and G. Boheim (1986) Journal of Membrane Biology, Vol. 93, pp. 111–132]. Ala 20 and Leu 20 dimers exhibit well‐defined ridges‐in‐grooves packing with helix crossing angles (Ω) of the order of +20°. Aib 20 α‐helix dimers are much more loosely packed, as evidenced by a wide range of Ω values and small helix‐helix interaction energies. However, when in a 3 10 conformation Aib 20 helices pack in three well‐defined parallel modes, with Ω ca. −15°, +5°, and 10°. Comparison of helix–helix interaction energies suggests that dimerization may favor the 3 10 conformation. P20, with 8 Aib residues, also shows looser packing of α‐helices. The results of these studies of hydrophobic helix dimers are analyzed in the context of the ridges‐in‐grooves packing model. Simulations are extended to dimers of alamethicin, and of an alamethicin derivative in which all Aib residues are replaced by Leu. This substitution has little effect on helix–helix packing. Rather, such interactions appear to be sensitive to interactions between polar side chains. Overall, the results suggest that Aib may modulate the packing of simple hydrophobic helices, in favor of looser interactions. For more complex amphipathic helices, interactions between polar side chains may be more critical. © 1995 John Wiley & Sons, Inc.