111,957 research outputs found
Theoretical Study of Vibrational Properties of Peptides: Force Fields in Comparison and Ab Initio Investigation
No full textInfrared (IR) spectroscopy is a valuable tool to obtain information about protein secondary structure. The far-infrared (FIR) spectrum is characterized by a complex combination of different molecular contributions which, for small molecules, may be interpreted with the help of quantum-mechanical (QM) calculations. Unfortunately, the high computational cost of QM calculations makes them inapplicable to larger molecules, such as proteins and peptides. In this work, we present a theoretical study on the secondary structure, molecular properties, and vibrational spectra of different peptides, using both a classical and a QM approach. Our results show that the amide I main peak value, and related quantities, such as dipole strength (DS) and transition dipole moment (TDM), depends on protein secondary structure; in particular, from QM calculations arises that α-rich molecular systems present lower intensities than β-rich ones. Furthermore, it is possible to decouple and identify the intensity of the different contributions of the inter- and intra-molecular motions which characterize the FIR spectrum, starting from the results obtained with QM calculations
Monitoring Insulin-Aggregated Structures in the Presence of Epigallocatechin-3-gallate and Melatonin by Molecular Dynamics Simulations
No full textIn the present work we illustrate the results of classical molecular dynamics simulations of model systems composed of six insulin molecules in water in the presence and in the absence of either epigallocatechin-3-gallate or melatonin molecules. For each model system, we performed three independent simulations (replicas) to study the aggregate formation dynamics and insulin interaction with epigallocatechin-3-gallate and melatonin. We find that melatonin is less stably close to insulin with respect to epigallocatechin-3-gallate, which interacts more stably with insulin molecules and mainly with insulin's chain B hydrophobic residues. We observe that the shape of the insulin-aggregated structures in the three model systems is different and depends on whether epigallocatechin-3-gallate is present or not. Simulations show that in the absence of epigallocatechin-3-gallate, insulin molecules tend to form linear aggregates, while in the presence of epigallocatechin-3-gallate, aggregates display a globular shape, less prone to form fibril structures
A Colding-Minicozzi stability inequality and its applications
No full textWe consider operators
L
L
acting on functions on a Riemannian surface,
Σ
\Sigma
, of the form
Here
Δ
\Delta
is the Laplacian of
Σ
\Sigma
,
V
V
a nonnegative potential on
Σ
\Sigma
,
K
K
the Gaussian curvature and
a
a
is a nonnegative constant.
Such operators
L
L
arise as the stability operator of
Σ
\Sigma
immersed in a Riemannian
3
−
3-
manifold with constant mean curvature (for particular choices of
V
V
and
a
a
). We assume that
L
L
is nonpositive acting on functions compactly supported on
Σ
\Sigma
and we obtain results in the spirit of some theorems of Fischer-Colbrie-Schoen, Colding-Minicozzi and Castillon. We extend these theorems to
a
≤
1
/
4
a \leq 1/4
. We obtain results on the conformal type of
Σ
\Sigma
and a distance (to the boundary) lemma.</p
Tuning force-field parameters by pressure measurements in micro-canonical simulations
No full textWe show that the dramatic dependence of pressure on the parameters of the intermolecular potential can be exploited to tune them to their best values. We support the viability of this strategy by a careful study of a fully diffusive Lennard-Jones fluid, showing that Lennard-Jones parameters can be easily optimized to better than a 1% accuracy
Thioflavin T templates amyloid β(1-40) conformation and aggregation pathway
No full textAβ(1-40) peptide supramolecular assembly and fibril formation processes are widely recognized to have direct implications in the progression of Alzheimer's disease. The molecular basis of this biological process is still unknown and there is a strong need of developing effective strategies to control the occurring events. To this purpose the exploitation of small molecules interacting with Aβ aggregation represents one of the possible routes. Moreover, the use specific labeling has represented so far one of the most common and effective methods to investigate such a process. This possibility in turn rests on the reliability of the probe/labels involved. Here we present evidences of the effect of Thioflavin T (ThT), a worldwide used fluorescent dye to monitor amyloid growth, on the Aβ(1-40) conformation, stability and aggregation. By combining experimental information and Molecular Dynamics simulation results, we show that the presence of ThT in solution affects peptide conformation inducing peculiar supramolecular association. In particular ThT interactions with specific Aβ(1-40) residues promote a rigid partially-folded conformation which shifts the balance between different species in solution toward a more aggregation-prone ensemble of peptides, leading to aggregation. Our findings suggest ways for developing strategies to reverse and block aggregation or to stimulate supramolecular assembly and consequently reduce the presence of transient oligomers. This investigation underlines the need of developing label-free techniques for unbiased quantitative studies of Aβ(1-40) aggregation processes
The role of metals in amyloid aggregation: A test case for ab initio simulations
No full textFirst principle ab initio molecular dynamics simulations of the Car-Parrinello type have proved to be of invaluable help in understanding the microscopic mechanisms of chemical bonding both in solid state physics and in structural biophysics. In this work we present as test cases the study of the Cu coordination mode in two especially important examples: Prion protein and beta-amyloids. Using medium size PC-clusters as well as larger parallel platforms, we are able to deal with systems comprising 300 to 500 atoms and 1000 to 1500 electrons for as long as 2 - 3 ps. We present structural results which confirm indications coming from NMR and XAS data
The Role of Metals in Misfolding and Aggregation Processes: X-ray Spectroscopy and Numerical Simulations
No full textMolecular dynamics and hybrid Monte Carlo simulations of a sodium bis(2-ethylhexyl)-sulfosuccinate reverse micelle
No full textThe bis(2-ethylhexyl)sulfosuccinate (AOT) reverse micelle is a nanometer-sized quasispherical aggregate that can dissolve water in its interior. This feature makes a reverse micelle a valuable model system for the study of "hydration water", i.e. water confined in the proximity of polar and ionic groups. We present a first study of the structural and thermodynamical properties of a system formed by 2048 CCl4 molecules in which an AOT reverse micelle, including its internal hydration water and Na+ counterions, is contained. CCl4 equilibrium configurations are obtained from a very long hybrid Monte Carlo simulation of a cubic box of 256 CCl4 molecules which is then duplicated in all three dimensions. The whole system is successively equilibrated using a standard molecular dynamics simulation algorithm
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