Rational Design of Protein-Specific Folding Modifiers.

Protein-folding can go wrong and , with significant consequences for the living organism and the pharmaceutical industry, respectively. Here we propose a design principle for small-peptide-based protein-specific folding modifiers. The principle is based on constructing a "xenonucleus", which is a prefolded peptide that mimics the folding nucleus of a protein.

The Molecular Mechanism of Domain Swapping of the C-Terminal Domain of the SARS-Coronavirus Main Protease.

In three-dimensional domain swapping, two protein monomers exchange a part of their structures to form an intertwined homodimer, whose subunits resemble the monomer. Several viral proteins domain swap to increase their structural complexity or functional avidity. The main protease (M) of the severe acute respiratory syndrome (SARS) coronavirus proteolyzes viral polyproteins and has been a target for anti-SARS drug design.

The Sensitivity of Computational Protein Folding to Contact Map Perturbations: The Case of Ubiquitin Folding and Function.

Ubiquitin is a small model protein, commonly used in protein folding experiments and simulations. We simulated ubiquitin using a well-tested structure-based model coarse-grained to a C level (C-SBM) and found that the simulated folding route did not agree with the experimentally observed one. Simulating the C-SBM with a cutoff contact map, instead of a screened contact map, switched the folding route with the new route matching the experimental route.

Intrinsic Disorder in a Well-Folded Globular Protein.

The folded structure of the heterodimeric sweet protein monellin mimics single-chain proteins with topology β1-α1-β2-β3-β4-β5 (chain A: β3-β4-β5; chain B: β1-α1-β2). Furthermore, like naturally occurring single-chain proteins of a similar size, monellin folds cooperatively with no detectable intermediates. However, the two monellin chains, A and B, are marginally structured in isolation and fold only upon binding to each other.