[Conformational state and mechanism of functioning of gramicidin A].

Theoretical conformational analysis of the antibiotic gramicidin A HCO--L-Val--Gly--L-Ala--D-leu--L-Ala--D-Val--L-Val--D-Val--(L-Trp--D-Leu)3--L-Trp--NHCH2CH2OH has been carried out by stagewise computations of a serie of LD penta-decapeptide analogs, which approximated the structure of the natural compound at the final stage. The potential surface of the LD-peptide skeleton of the gramicidin molecule is shown to predetermine the existence of a set of pi4LD--Pi6LD structures. Low-energy helical structures with no hydrogen bonds have also been revealed, which are due to compensational relations between hydrogen bonding and nonbonded energies. Inclusion of D-Val into the amino acid sequence discriminate against alpha-helix, while Trp and Leu residues contribute to a formation of pi4LD and pi6LD helices and to a reduction of energy differences between them. Conformational properties and geometrical parameters of the lowest-energy helical structures of gramicidin provide transport of protones and of all alkali metal ions. A mechanism of cation transportation through the gramicidin trans-membrane channel is discussed.