Quantum Interactions Between Non-Perturbative Vacuum Fields

We develop an approach to investigate the non-perturbative dynamics of quantum field theories, in which specific vacuum field fluctuations are treated as the low-energy dynamical degrees of freedom, while all other vacuum field configurations are explicitly integrated out from the path integral. We show how to compute the effective interaction between the vacuum field degrees of freedom both perturbatively (using stochastic perturbation theory) and fully non-perturbatively (using lattice field theory simulations). The present approach holds to all orders in the couplings and does not rely on the semi-classical approximation.Comment: 15 pages, 4 figure

The Role of Non-native Interactions in the Folding of Knotted Proteins

Stochastic simulations of coarse-grained protein models are used to investigate the propensity to form knots in early stages of protein folding. The study is carried out comparatively for two homologous carbamoyltransferases, a natively-knotted N-acetylornithine carbamoyltransferase (AOTCase) and an unknotted ornithine carbamoyltransferase (OTCase). In addition, two different sets of pairwise amino acid interactions are considered: one promoting exclusively native interactions, and the other additionally including non-native quasi-chemical and electrostatic interactions. With the former model neither protein show a propensity to form knots. With the additional non-native interactions, knotting propensity remains negligible for the natively-unknotted OTCase while for AOTCase it is much enhanced. Analysis of the trajectories suggests that the different entanglement of the two transcarbamylases follows from the tendency of the C-terminal to point away from (for OTCase) or approach and eventually thread (for AOTCase) other regions of partly-folded protein. The analysis of the OTCase/AOTCase pair clarifies that natively-knotted proteins can spontaneously knot during early folding stages and that non-native sequence-dependent interactions are important for promoting and disfavoring early knotting events.Comment: Accepted for publication on PLOS Computational Biolog