Natural springs: Prediction of the structure and mechanical response of biomolecular chains

In this paper we report first the application of the adaptive simulated annealing (ASA) global optimization method for structure determination of biomolecules, using the Empirical Conformation Energy Program for Peptides (ecepp/2) potential. A dominant right-handed alpha-helical conformation is found for an (l-Ala) model, and the approach is noted to be an efficient and robust algorithm for conformational analysis. The prediction of biomolecular structure then enables the evaluation of the mechanical response of any biomolecular chain. In particular, in this study we compare on a theoretical basis the ‘spring-like’ microscopic mechanical response of alpha-helical biopolymers having a reinforcing intra-molecular hydrogen-bonding network to analogous synthetic extended-chain polymers. The theoretical verification of the absence of compressive buckling in biopolymer chains with alpha-helical structures rationalizes the molecular elasticity and resistance to ‘kinking’ of alpha-helical strands, and hence the apparent prevalence in nature of such coiled coils. ew understanding of the structure-to-function relationships in biopolymers may also explain, in part, the pivotal role of the alphahelix in biological systems as a requirement for superior compressive mechanical properties. Indeed, by developing a combination of approaches for the prediction of structure and the mechanical response of biomolecular chains, we gain new guidance for the synthesis of motifs consistent with molecular frameworks optimized by nature.