Internal and external alkali ion complexes of enniatin B: an empirical force field analysis

Abstract

The empirical force field method is used to calculate conformations and energies of the natural ion carrier enniatin B (EnB) and its alkali ion complexes. Solvent effects are circumvented by focusing the study on conformational characteristics and trends in ionophoric behavior, which do not require an evaluation of solvent interactions. A few calculated, low-energy conformations of the EnB ring are presented. The C3-symmetric conformation of EnB is analyzed in detail. Its rotational isomeric states of the isopropyl side chains are found to interact strongly with its carbonyl and N-methyl groups, thus restricting significantly the flexibility of EnB's skeletal ring. Two kinds of 1 : 1 EnB-ion complexes are obtained: internal and external. In internal complexes, the ion is located at or near the center of an octahedral cavity formed by the six carbonyls of EnB and binds to all these carbonyls. The large strain energy imposed on the ligand by bending the carbonyls inward destabilizes the internal binding. E n n i a t i n s are natural ion carriers whose biological functions are determined by their ability to transport cations across lipid bilayer membranes. Enniatins, and particularly enniatin B,' Abbreviations: EnB, enniatin B; (LacAla)3, EnB methyl side chain analogue [ (-~-lactyl-~-N-methylalanyl)~]; Lac6, EnB hexalactyl analogue [ (-D-laCtyl-L-laCtyl)3].

Enniatin B and Valinomycin as Ion Carriers: An Empirical Force Field Analysis

“…However, there is a difference between EnB disfavoring Li+ and VM disfavoring Na+ which is worth mentioning. In the first case, since Li+ is unable to pull in and bind to all six carbonyls, it binds asymmetrically to only three of them (5,6). In contrast, since the ester carbonyls of VM already point inward to the center of the cavity, Na+ is able to bind to all of them.…”

“…The theoretical and computational considerations about the design and analysis of macrocyclic ion-carriers in general and EnB in particular have been discussed in detail (5,6). The same considerations are applicable to VM, with the appropriate Downloaded by [Rutgers University] at 13:32 07 April 2015 adaptation to its size, which is twice that of EnB.…”

“…The two numbers of each pair refer to the carbonyls of the D-HylV and L-NMVal residues of EnB, or of the D-Val and L-Val residues of VM, respectively. bCalculated values taken from Lifson et al (5). ex-ray structure of Newpert-Laves and Dobler (10).…”

Effects of crystal packing and hydration on the conformation of enniatin B

“…The computer program used for the empirical force-field calculations (Lifson et al, 1983(Lifson et al, , 1984 was augmented to include interactions with neighbouring molecules of a crystal by adding subroutines taken from program MCA + QCPP/PI (Huler, Warshel & Sharon, 1974;Huler, Sharon & Warshel, 1976;Warshel 1977). The Coulombic and Lennard-Jones 6-9 potential functions for the intermolecular interactions were the same as those employed in the intramolecular interactions, and were taken between each atom of the main molecule and each atom of its 24 nearest neighbours (see below).…”

The Crystal Structure of Enniatin B

“…Conformations P and N were investigated by empirical energy minimization [8] (using an analoguous compound in which all i-Pr groups were replaced by CH, and conformation P also by quantum mechanical calculations [ 161. Recently an extended force-field calculation by LiJson et al [9] resulted in a minimum energy conformation with C, symmetry similar to form P. An early crystal-structure analysis of a KI complex of enniatin B [lo] had to make use of poor quality crystals. Therein, the disc-shaped cation complexes are stacked along the hexagonal axis and the anions are statistically distributed in the channels between these stacks.…”