A Molecular-Dynamics Simulation Study of the Conformational Preferences of Oligo(3-hydroxyalkanoic acids) in Chloroform Solution

The GROMOS96 molecular-dynamics (MD) program and force field was used to calculate the conformations at 298 K in CHCl3 solution of two hexakis(3-hydroxyalkanoic acids). One consists of (R)-3-hydroxybutanoate (HB) residues only: H-(OCH(Me)-CH2-CO)6-OH (1). The other one carries the side chains of valine, alanine, and leucine: H-(OCH(CHMe2)CH2-CO-O-CH(Me)-CH2-CO-O-CH(CH2 CHMe2)-CH2-CO)2-OH (2), with homochiral 3-hydroxyalkanoate (HA) moieties. In both cases, the conformational equilibria were sampled 2500 times for 25 ns. Other than clusters of arrangements with inter-residual hydrogen bonding (between the O- and C-terminal OH and COOH groups, and with chain-bound ester carbonyl O-atoms; Fig. 6), there are no preferred backbone conformations in which the molecules 1 and 2 spend more than 5% of the time. Specifically, neither the 21- nor the 31-helical conformation of the oligoester backbone (found in stretched fibers, in lamellar crystallites, and in single crystals of polymers PHB and of oligomers OHB) is sampled to any significant extent (Fig. 8 and 9), in spite of the high population, in both oligomers, of the (-)-synclinal conformation around the C(2)-C(3) bond (angle 2 in Fig. 2). In contrast to -oligopeptides, for which strongly preferred secondary structures are found after a few ns, and for which the number of conformations levels off with time, the number of conformational clusters of the corresponding oligoesters found by our force-field MD calculations increases steadily over the observation time of 25 ns (Fig. 5). Thus, the conclusion from biological and physical-chemical studies, according to which the PHB chain is extremely flexible, is confirmed by our computational investigation: in CHCl3 solution, the hexakis(3-hydroxyalkanoate) chain samples its conformational space randomly!