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Here we present an approximate analytical theory for the relationship between a protein structure's contact matrix and the shape of its energy spectrum in amino acid sequence space. We demonstrate a dependence of the number of sequences of low energy in a structure on the eigenvalues of the structure's contact matrix, and then use a Monte Carlo simulation(More)
Modeling the inherent flexibility of the protein backbone as part of computational protein design is necessary to capture the behavior of real proteins and is a prerequisite for the accurate exploration of protein sequence space. We present the results of a broad exploration of sequence space, with backbone flexibility, through a novel approach: large-scale(More)
Self-replication is a capacity common to every species of living thing, and simple physical intuition dictates that such a process must invariably be fueled by the production of entropy. Here, we undertake to make this intuition rigorous and quantitative by deriving a lower bound for the amount of heat that is produced during a process of self-replication(More)
Despite the spontaneity of some in vitro protein-folding reactions, native folding in vivo often requires the participation of barrel-shaped multimeric complexes known as chaperonins. Although it has long been known that chaperonin substrates fold upon sequestration inside the chaperonin barrel, the precise mechanism by which confinement within this space(More)
We systematically reviewed research examining the association between gestational diabetes (GDM) and childhood overweight and obesity. We identified studies from three sources: (1) a PubMed search of articles published between January 1990-January 2011, (2) reference lists of publications from the PubMed search, and (3) reference lists of review articles.(More)
We investigate the effect of time-dependent noise on the shape of a morphogen gradient in a developing embryo. Perturbation theory is used to calculate the deviations from deterministic behavior in a simple reaction-diffusion model of robust gradient formation, and the results are confirmed by numerical simulation. It is shown that such deviations can(More)
Noting that the glutamine (Q) amino acid side-chain bears a striking resemblance to urea, the chemical denaturant, we argue on biophysical grounds that polyQ chains should possess a potent denaturant activity. Using live-cell confocal microscopy, we demonstrate that the surface of a polyQ inclusion denatures cytosolic proteins by binding and trapping them(More)
Chaperonins engulf other proteins and accelerate their folding by an unknown mechanism. Here, we combine all-atom molecular dynamics simulations with data from experimental assays of the activity of the bacterial chaperonin GroEL to demonstrate that a chaperonin's ability to facilitate folding is correlated with the affinity of its interior surface for(More)
Near equilibrium, small current fluctuations are described by a Gaussian distribution with a linear-response variance regulated by the dissipation. Here, we demonstrate that dissipation still plays a dominant role in structuring large fluctuations arbitrarily far from equilibrium. In particular, we prove a linear-response-like bound on the large deviation(More)
The mechanism by which the aqueous cosolvents guanidinium chloride and urea denature proteins is a matter of controversy. Here, we use all-atom molecular dynamics simulations to study the effect of both denaturants on the dewetting of water confined between nanoseparated hydrophobic plates. It is found that the denaturants inhibit the onset of dewetting, so(More)