55 research outputs found
An insight into the inhibitory selectivity of 4-(Pyrazol- 4-yl)-pyrimidines to CDK4 over CDK2
<p>Revealing selectivity mechanism of cyclin-dependent kinases (CDK) and their inhibitors is an important issue to develop potential anticancer drugs. The substituted 4-(Pyrazol-4-yl)-pyrimidines are potent inhibitors of CDK4 but not of the highly homologous CDK2. In order to reveal the inhibitory selectivity of these inhibitors to CDK4 over CDK2, we select one of substituted 4-(Pyrazol-4-yl)-pyrimidines as a representative (marked as A1 hereunder) and perform molecular docking, molecular dynamics simulations and binding free energy analysis for CDK4/A1 and CDK2/A1, respectively. The electrostatic and van der Waals (vdW) interactions of the A1 inhibitor with CDK4/CDK2 are discussed. The computed binding free energies based on the MM-PBSA method are consistent with experimental bioactivity ranking of A1 inhibitor to CDK4/CDK2. On the other hand, the conformational characteristics of CDK2 and CDK4 induced by A1 inhibitor are analysed and revealed. Results demonstrate that the vdW interactions considerably contribute to binding of CDK4/CDK2 with A1 inhibitor and are similar in size. The hydrogen bonding between A1 inhibitor and CDK4/CDK2 is considerably favourable to the binding, in which the hydrogen bond between the NH group of the pyrazole group of A1 and the residue Asp158 of CDK4 plays a crucial role in inhibitory selectivity of A1 inhibitor to CDK4 over CDK2. The electrostatic interaction energy differences between the corresponding residues of CDK4/A1 and CDK2/A1 confirm the above inference. The conformational changes of CDK2 and CDK4 induced by A1 inhibitor influence the selectivity of A1 inhibitor to CDK4/CDK2.</p
Characteristics and Distribution of Phosphorus in Surface Sediments of Limnetic Ecosystem in Eastern China
<div><p>Phosphorus (P) is an essential nutrient for aquatic organisms; however, excessive P inflow to limnetic ecosystems can induce eutrophication. P concentrations in the rivers, wetlands and lakes of Eastern China have been amplified by fertilizer and sewage inputs associated with the development of industry and agriculture. Yet, knowledge of the distribution and speciation of P is lacking at the regional scale. We determined the distribution and speciation of P in limnetic ecosystems in Eastern China using Standards, Measurements and Testing (SMT) and phosphorus nuclear magnetic resonance (<sup>31</sup>P-NMR). The results indicate that P pollution in surface sediments was serious. Inorganic P (Pi) was the primary drive of variation in total P (TP) among different river systems, and Pi accounted for 71% to 90% of TP in surface sediment in Eastern China. Also, the concentrations of TP and Pi varied among watersheds and Pi primarily drove the variation in TP in different watersheds. Sediments less than 10-cm deep served as the main P reservoir. Environmental factors affect the speciation and origin of P. NaOH-Pi, HCl-Pi and organic P (Po) were related to pH accordingly at the regional scale. The physicochemical properties of sediments from different limnetic ecosystems affect the P speciation. HCl-Pi was higher in wetland sediments than in riverine and lake sediments in Eastern China. Conversely, NaOH-Pi was lowest in wetland sediments. Total Po concentration was lower in riverine sediments than in other sediments, but Mono-P was higher, with an average concentration of 48 mg kg<sup>−1</sup>. Diesters-P was highest in lake sediments. By revealing the regional distribution of TP, Pi and Po, this study will support eutrophication management in Eastern China.</p></div
Investigation of Structural, Thermal, and Dynamical Properties of Pd–Au–Pt Ternary Metal Nanoparticles Confined in Carbon Nanotubes Based on MD Simulation
We
apply molecular dynamics (MD) simulations to investigate structural,
thermal, and dynamical properties of Pd–Au–Pt trimetallic
nanoparticles confined in armchair single-walled carbon tubes ((<i>n</i>,<i>n</i>)-SWNTs). The metal–carbon interactions
are described by a Lennard-Jones (LJ) potential, while the metal–metal
interactions are represented by the second-moment approximation of
the tight-binding (TB-SMA) potentials. Results illustrate that the
confined Pd–Au–Pt metal nanoparticles appear to be of
cylindrical multishelled structure, similar to those of gold (or Au–Pt)
nanoparticles confined in SWNT and different from free Pd–Au–Pt
nanoparticles or bulk gold. For each confined Pd–Au–Pt
nanoparticle, gold atoms preferentially accumulate near the tube center,
while Pt atoms preferentially distribute near the tube wall. These
results are in qualitative agreement with previous observations on
Au–Pt nanoparticles confined in SWNT. Importantly, Pd atoms
disperse thorough the confined Pd–Au–Pt nanoparticle,
which is consistent with caltalytic observations in experiment. The
melting temperatures of the confined Pd–Au–Pt nanoparticles
are controlled by platinum with greater cohesive energy. The melting
temperatures of the confined Pd–Au–Pt nanoparticles
are significantly higher than those of the free Pd–Au–Pt
nanoparticles, which are caused by the confined interaction of SWNT.
Some important dynamic results are obtained in terms of the classical
nucleation theory
Sediment characteristics in different freshwater ecosystems in Eastern China.
<p>Sediment characteristics in different freshwater ecosystems in Eastern China.</p
Partial <sup>31</sup>P-NMR spectra of NaOH-EDTA extracts of the surface sediments in freshwater ecosystems of Eastern China.
<p>A: phosphonate; B: orthophosphate; C: orthophosphate monoesters; D: orthophosphate diesters; E: phospholipids; F: deoxyribonucleic acids; G: pyrophosphates; H: polyphosphates.</p
P components in surface sediment determined by SMT fractionation and <sup>31</sup>P-NMR.
<p>DNA-P: deoxyribonucleic acids (orthophosphate diesters); Lipids-P: phospholipids (orthophosphate diesters); Mono-P: orthophosphate monoesters; Ortho-P: orthophosphate; Phon-P: phosphonates; Pyro-P: pyrophosphates.</p
Biplot of sediment properties and sediment P among sample sites.
<p>Biplot of sediment properties and sediment P among sample sites.</p
The distribution of P in freshwater ecosystems of Eastern China.
<p>A: TP concentration in surface sediment, where the coefficient is P content per 500 mg kg<sup>−1</sup> [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156488#pone.0156488.ref028" target="_blank">28</a>]. B: Average concentrations of TP, Pi and Po in different river systems. C: TP, Pi and Po concentrations in river and lake sediment cores in Eastern China.</p
Relationships between pH and NaOH-Pi, HCl-Pi, LOI and Po in sediments of Eastern China.
<p>NaOH-Pi, LOI and MUP were negatively correlated with pH (<i>p</i> < 0.01, n = 89); HCl-Pi was positively correlated with pH (<i>p</i> < 0.01, n = 89).</p
Some Insight into Stability of Amorphous Poly(ethylene glycol) Dimethyl Ether Polymers Based on Molecular Dynamics Simulations
PolyÂ(ethylene glycol) dimethyl ether
(PEGDME) polymers are widely
used as drug solid dispersion reagents. They can cause the amorphization
of drugs and improve their solubility, stability, and bioavailability.
However, the mechanism about why amorphous PEGDME 2000 polymer is
highly stable is unclear so far. Molecular dynamics (MD) simulation
is a unique key technique to solve it. In the current work, we systematically
investigate structure, aggregate state, and thermodynamic and kinetic
behaviors during the phase-transition processes of the PEGDME polymers
with different polymerization degree in terms of MD simulations. The
melting and glass-transition temperatures of the polymers are in good
agreement with experimental values. The amorphous PEGDME2000 exhibits
high stability, which is consistent with the recent experiment results
and can be ascribed to a combination of two factors, that is, a high
thermodynamic driving force for amorphization and a relatively low
molecular mobility
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