46 research outputs found
Transferable coarse-grained potential for protein folding and design
Protein folding and design are major biophysical problems, the solution of
which would lead to important applications especially in medicine. Here a novel
protein model capable of simultaneously provide quantitative protein design and
folding is introduced. With computer simulations it is shown that, for a large
set of real protein structures, the model produces designed sequences with
similar physical properties to the corresponding natural occurring sequences.
The designed sequences are not yet fully realistic and require further
experimental testing. For an independent set of proteins, notoriously difficult
to fold, the correct folding of both the designed and the natural sequences is
also demonstrated. The folding properties are characterized by free energy
calculations. which not only are consistent among natural and designed
proteins, but we also show a remarkable precision when the folded structures
are compared to the experimentally determined ones. Ultimately, this novel
coarse-grained protein model is unique in the combination of its fundamental
three features: its simplicity, its ability to produce natural foldable
designed sequences, and its structure prediction precision. The latter
demonstrated by free energy calculations. It is also remarkable that low
frustration sequences can be obtained with such a simple and universal design
procedure, and that the folding of natural proteins shows funnelled free energy
landscapes without the need of any potentials based on the native structure
A Coarse-Grained Approach to Protein Design: Learning from Design to Understand Folding
Computational studies have given a great contribution in building our current understanding of the complex behavior of protein molecules; nevertheless, a complete characterization of their free energy landscape still represents a major challenge. Here, we introduce a new coarse-grained approach that allows for an extensive sampling of the conformational space of a large number of sequences. We explicitly discuss its application in protein design, and by studying four representative proteins, we show that the method generates sequences with a relatively smooth free energy surface directed towards the target structures
JETSPIN: a specific-purpose open-source software for simulations of nanofiber electrospinning
We present the open-source computer program JETSPIN, specifically designed to
simulate the electrospinning process of nanofibers. Its capabilities are shown
with proper reference to the underlying model, as well as a description of the
relevant input variables and associated test-case simulations. The various
interactions included in the electrospinning model implemented in JETSPIN are
discussed in detail. The code is designed to exploit different computational
architectures, from single to parallel processor workstations. This paper
provides an overview of JETSPIN, focusing primarily on its structure, parallel
implementations, functionality, performance, and availability.Comment: 22 pages, 11 figures. arXiv admin note: substantial text overlap with
arXiv:1507.0701
Different regimes of the uniaxial elongation of electrically charged viscoelastic jets due to dissipative air drag
We investigate the effects of dissipative air drag on the dynamics of
electrified jets in the initial stage of the electrospinning process. The main
idea is to use a Brownian noise to model air drag effects on the uniaxial
elongation of the jets. The developed numerical model is used to probe the
dynamics of electrified polymer jets at different conditions of air drag force,
showing that the dynamics of the charged jet is strongly biased by the presence
of air drag forces. This study provides prospective beneficial implications for
improving forthcoming electrospinning experiments.Comment: 12 pages, 6 figure
In silico evidence that protein unfolding is as a precursor of the protein aggregation
We present a computational study on the folding and aggregation of proteins in an aqueous environment, as a function of its concentration. We show how the increase of the concentration of individual protein species can induce a partial unfolding of the native conformation without the occurrence of aggregates. A further increment of the protein concentration results in the complete loss of the folded structures and induces the formation of protein aggregates. We discuss the effect of the protein interface on the water fluctuations in the protein hydration shell and their relevance in the protein‐protein interaction
Limiting the valence: advancements and new perspectives on patchy colloids, soft functionalized nanoparticles and biomolecules
Limited bonding valence, usually accompanied by well-defined directional
interactions and selective bonding mechanisms, is nowadays considered among the
key ingredients to create complex structures with tailored properties: even
though isotropically interacting units already guarantee access to a vast range
of functional materials, anisotropic interactions can provide extra
instructions to steer the assembly of specific architectures. The anisotropy of
effective interactions gives rise to a wealth of self-assembled structures both
in the realm of suitably synthesized nano- and micro-sized building blocks and
in nature, where the isotropy of interactions is often a zero-th order
description of the complicated reality. In this review, we span a vast range of
systems characterized by limited bonding valence, from patchy colloids of new
generation to polymer-based functionalized nanoparticles, DNA-based systems and
proteins, and describe how the interaction patterns of the single building
blocks can be designed to tailor the properties of the target final structures
Role of water in the selection of stable proteins at ambient and extreme thermodynamic conditions
Proteins that are functional at ambient conditions do not necessarily work at extreme conditions of temperature T and pressure P. Furthermore, there are limits of T and P above which no protein has a stable functional state. Here, we show that these limits and the selection mechanisms for working proteins depend on how the properties of the surrounding water change with T and P. We find that proteins selected at high T are superstable and are characterized by a nonextreme segregation of a hydrophilic surface and a hydrophobic core. Surprisingly, a larger segregation reduces the stability range in T and P. Our computer simulations, based on a new protein design protocol, explain the hydropathy profile of proteins as a consequence of a selection process influenced by water. Our results, potentially useful for engineering proteins and drugs working far from ambient conditions, offer an alternative rationale to the evolutionary action exerted by the environment in extreme conditions