The formation of amyloid aggregates upon protein misfolding is related to several devastating degenerative diseases. propensities different sequences aggregate into amyloids, how they are enhanced by pathogenic mutations, the presence aggregation hot spots stabilizing pathological interactions, establishing cross-amyloid interactions between co-aggregating proteins, all rely at molecular level on stability cross-beta structure. Our redesigned server, PASTA 2.0, provides a versatile platform...

Proteins have coevolved with cellular environments to improve or preserve their functions, maintaining at the same time degree of hydrophobicity necessary fold correctly and enough solubility perform biological roles. Here, we study Escherichia coli proteome using a Pareto front analysis in solubility-hydrophobicity space. The results indicate existence optimal front, triangle whose vertices correspond archetypal proteins specialized distinct tasks, such as regulatory processes, membrane...

Many different proteins aggregate into amyloid fibrils characterized by cross-beta structure. beta-strands contributed distinct protein molecules are generally found in a parallel in-register alignment. Here, we describe the web server for novel algorithm, prediction of structure aggregation (PASTA), to predict most aggregation-prone portions and corresponding beta-strand inter-molecular pairing given input sequence. PASTA was previously shown yield results excellent agreement with available...

We present a simple physical model that demonstrates the native-state folds of proteins can emerge on basis considerations geometry and symmetry. show inherent anisotropy chain molecule, geometrical energetic constraints placed by hydrogen bonds sterics, hydrophobicity are sufficient to yield free-energy landscape with broad minima even for homopolymer. These correspond marginally compact structures comprising menu choose from house their native states in. Our results provide general...

The conversion from soluble states into cross-β fibrillar aggregates is a property shared by many different proteins and peptides was hence conjectured to be generic feature of polypeptide chains. Increasing evidence now accumulating that such assemblies are generally characterized parallel in-register alignment β-strands contributed distinct protein molecules. Here we assume universal mechanism responsible for β-structure formation deduce sequence-specific interaction energies between pairs...

Nanoparticles introduced in living cells are capable of strongly promoting the aggregation peptides and proteins. We use here molecular dynamics simulations to characterise detail process by which nanoparticle surfaces catalyse self-assembly into fibrillar structures. The simulation a system hundreds over millisecond timescale enables us show that mechanism involves first phase small structurally disordered oligomers assemble onto second they evolve highly ordered as their size increases.

It is currently believed that the atlas of existing protein structures faithfully represented in Protein Data Bank. However, whether this covers full universe all possible still a highly debated issue. By using sophisticated numerical approach, we performed an exhaustive exploration conformational space 60 amino acid polypeptide chain described with accurate all-atom interaction potential. We generated database around 30,000 compact folds at least secondary structure corresponding to local...

The folding of a protein towards its native state is rather complicated process. However there are empirical evidences that the time correlates with contact order, simple measure spatial organisation protein. Contact order related to average length main chain loops formed by amino acids which in contact. Here we argue kinetics can be influenced also entanglement may undergo within overall three dimensional structure. In explore such possibility, introduce novel descriptor, call "maximum...

Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots rare. Here, we reveal the existence of specific patterns adopted protein sequences and structures deal with backbone self-entanglement. A large scale analysis Protein Data Bank shows that loops significantly intertwined another chain portion typically closed weakly bound amino acids. Why is this...

The mechanical separation of a double helical DNA structure induced by forces pulling apart the two strands (``unzipping'') has been subject recent experiments. Analytical results are obtained within various models interacting pairs directed walks in $(1,1,\dots{},1)$ direction on hypercubic lattice, and phase diagram force-temperature plane is studied for variety cases. scaling behavior determined at both unzipping melting transitions. We confirm existence cold denaturation transition...

Abstract Motivation: Proteins with solenoid repeats evolve more quickly than non-repetitive ones and their periodicity may be rapidly hidden at sequence level, while still evident in structure. In order to identify these repeats, we propose here a novel method based on metric characterizing amino-acid properties (polarity, secondary structure, molecular volume, codon diversity, electric charge) using five previously derived numerical functions. Results: The spectra of the candidate sequences...

In protein structure prediction it is essential to score quickly and reliably large sets of models by selecting the ones that are closest native state. We here present a novel statistical potential constructed Bayesian analysis measuring few structural observables on set 500 experimental structures. Even though employing much less parameters than current state-of-the-art methods, our capable discriminating with an unprecedented reliability state in misfolded same protein. also introduce new...

The devising of efficient concerted rotation moves that modify only selected local portions chain molecules is a long studied problem. Possible applications range from speeding the uncorrelated sampling polymeric dense systems to loop reconstruction and structure refinement in protein modeling. Here, we propose validate, on few pedagogical examples, novel numerical strategy generalizes notion rotation. usage Denavit-Hartenberg parameters for description allows all possible choices subset...

Abstract The presence of knots has been observed in a small fraction single-domain proteins and related to their thermodynamic kinetic properties. exchanging identical structural elements, typical domain-swapped proteins, makes such dimers suitable candidates validate the possibility that mutual entanglement between chains may play similar role for protein complexes. We suggest is captured by linking number. This represents, two closed curves, number times each curve winds around other. show...

A conceptual framework for understanding the protein folding problem has remained elusive in spite of many significant advances. We show that geometrical constraints imposed by chain connectivity, compactness, and avoidance steric clashes can be encompassed a natural way using three-body potential lead to selection structure space, independent chemical details. Strikingly, secondary motifs such as hairpins, sheets, helices, which are building blocks folds, emerge chosen structures segments...

We study a physical system which, while devoid of the complexity one usually associates with proteins, nevertheless displays remarkable array protein-like properties. The constructive hypothesis that this striking resemblance is not accidental leads only to unified framework for understanding protein folding, amyloid formation and interactions but also has implications natural selection.

Human transthyretin (TTR) is an amyloidogenic protein whose mild amyloidogenicity enhanced by many point mutations affecting considerably the amyloid disease phenotype. To ascertain whether high potential of TTR variants may be explained on basis conformational change hypothesis, aim this work was to determine structural alterations for five crystallized under native and/or destabilizing (moderately acidic pH) conditions. While at pH changes more significant because a higher local...

We show that a framework derived from the common character of globular proteins can be used to understand design protein sequences, behavior intrinsically unstructured proteins, and formation amyloid fibrils in unified manner. Our studies provide compelling support for idea native-state structures, structures adopted by on binding as well those aggregates, all reside physical state matter which free energy landscape is sculpted not specific sequence amino acids, but rather considerations...

We present a maximum entropy approach for inferring amino acid interactions in proteins subject to constraints pertaining the mean numbers of various types equilibrium contacts given sequence or set sequences. have carried out several kinds tests two-dimensional lattice model with just two acids very promising results. also show that method works well even when are not known and therefore can be applied real proteins.

Bacterial communities undergo collective behavioural switches upon producing and sensing diffusible signal molecules; a mechanism referred to as Quorum Sensing (QS). Exemplarily, biofilm organic matrices are built concertedly by bacteria in several environments. QS scope bacterial ecology has been debated for over 20 years. Different perspectives counterpose the role of density reporter populations that local environment diffusivity probe individual cells. Here we devise model system where...