The Role of Spin Anisotropy in the Unbinding of Interfaces

We study the ground state of a classical X-Y model with $p \ge 3$-fold spin anisotropy $D$ in a uniform external field, $H$. An interface is introduced into the system by a suitable choice of boundary conditions. For large $D$, as $H \to 0$, we prove using an expansion in $D^{-1}$ that the interface unbinds from the surface through an infinite series of layering transitions. Numerical work shows that the transitions end in a sequence of critical end points.Comment: 7 pages RevTeX, plus 1 postscript figure available from the authors OUTP-94-41

A novel iterative strategy for protein design

We propose and discuss a novel strategy for protein design. The method is based on recent theoretical advancements which showed the importance to treat carefully the conformational free energy of designed sequences. In this work we show how computational cost can be kept to a minimum by encompassing negative design features, i.e. isolating a small number of structures that compete significantly with the target one for being occupied at low temperature. The method is succesfully tested on minimalist protein models and using a variety of amino acid interaction potentials.Comment: 9 pages, 8 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

Elucidation of the disulfide folding pathway of hirudin by a topology-based approach

A theoretical model for the folding of proteins containing disulfide bonds is introduced. The model exploits the knowledge of the native state to favour the progressive establishment of native interactions. At variance with traditional approaches based on native topology, not all native bonds are treated in the same way; in particular, a suitable energy term is introduced to account for the special strength of disulfide bonds (irrespective of whether they are native or not) as well as their ability to undergo intra-molecular reshuffling. The model thus possesses the minimal ingredients necessary to investigated the much debated issue of whether the re-folding process occurs through partially structured intermediates with native or non-native disulfide bonds. This strategy is applied to a context of particular interest, the re-folding process of Hirudin, a thrombin-specific protease inhibitor, for which conflicting folding pathways have been proposed. We show that the only two parameters in the model (temperature and disulfide strength) can be tuned to reproduce well a set of experimental transitions between species with different number of formed disulfide. This model is then used to provide a characterisation of the folding process and a detailed description of the species involved in the rate-limiting step of Hirudin refolding.Comment: 14 pages, 9 figure

Topological jamming of spontaneously knotted polyelectrolyte chains driven through a nanopore

The advent of solid state nanodevices allows for interrogating the physico-chemical properties of a polyelectrolyte chain by electrophoretically driving it through a nanopore. Salient dynamical aspects of the translocation process have been recently characterized by theoretical and computational studies of model polymer chains free from self-entanglement. However, sufficiently long equilibrated chains are necessarily knotted. The impact of such topological "defects" on the translocation process is largely unexplored, and is addressed in this study. By using Brownian dynamics simulations on a coarse-grained polyelectrolyte model we show that knots, despite being trapped at the pore entrance, do not "per se" cause the translocation process to jam. Rather, knots introduce an effective friction that increases with the applied force, and practically halts the translocation above a threshold force. The predicted dynamical crossover, which is experimentally verifiable, is of relevance in applicative contexts, such as DNA nanopore sequencing.Comment: 6 pages; 7 figure

Methyl 9-(1-methyl-1H-indol-3-yl)-9-oxononanoate

Methyl 9-(1-methyl-1H-indol-3-yl)-9-oxononanoate was synthesized using Friedel-Crafts acylation between N-methyl indole and methyl 9-chloro-9-oxononanoate. The structure of the newly synthesized compound was elucidated using H-1-NMR, C-13-NMR, NOESY-1D, ESI-MS, FT-IR, and UV-Vis spectroscopy