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Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop offers an insightful overview of the understanding of the mechanistic foundations of allostery, gained from computational and experimental analyses of real protein systems and model systems. Various practical applications are illustrated. [ABSTRACT FROM AUTHOR]

Summary: Molecular dynamics simulations of the RNA tetraloop 5′-CGCUUUUGCG-3′ with high melting temperature and significant conformational heterogeneity in explicit water solvent are presented and compared to NMR studies. The NMR data allow for a detailed test of the theoretical model, including the quality of the force field and the conformational sampling. Due to the conformational heterogeneity of the tetraloop, high temperature (350 K) and locally enhanced sampling simulations need to be invoked. The Amber98 force field leads to a good overall agreement with experimental data. Based on NMR data and a principal component analysis of the 350 K trajectory, the dynamic structure of the tetraloop is revealed. The principal component free energy surface exhibits four minima, which correspond to well-defined conformational structures that differ mainly by their base stacking in the loop region. No correlation between the motion of the sugar rings and the stacking dynamics of the loop bases is found. [Copyright &y& Elsevier]