246 research outputs found
Resolution-Adapted All-Atomic and Coarse-Grained Model for Biomolecular Simulations
We develop here an adaptive multiresolution
method for the simulation
of complex heterogeneous systems such as the protein molecules. The
target molecular system is described with the atomistic structure
while maintaining concurrently a mapping to the coarse-grained models.
The theoretical model, or force field, used to describe the interactions
between two sites is automatically adjusted in the simulation processes
according to the interaction distance/strength. Therefore, all-atomic,
coarse-grained, or mixed all-atomic and coarse-grained models would
be used together to describe the interactions between a group of atoms
and its surroundings. Because the choice of theory is made on the
force field level while the sampling is always carried out in the
atomic space, the new adaptive method preserves naturally the atomic
structure and thermodynamic properties of the entire system throughout
the simulation processes. The new method will be very useful in many
biomolecular simulations where atomistic details are critically needed
Pitfall in Quantum Mechanical/Molecular Mechanical Molecular Dynamics Simulation of Small Solutes in Solution
Developments in computing hardware
and algorithms have made direct
molecular dynamics simulation with the combined quantum mechanical/molecular
mechanical methods affordable for small solute molecules in solution,
in which much improved accuracy can be obtained via the quantum mechanical
treatment of the solute molecule and even sometimes water molecules
in the first solvation shell. However, unlike the conventional molecular
mechanical simulations of large molecules, e.g., proteins, in solutions,
special care must be taken in the technical details of the simulation,
including the thermostat of the solute/solvent system, so that the
conformational space of the solute molecules can be properly sampled.
We show here that the common setup for classical molecular mechanical
molecular dynamics simulations, such as the Berendsen or single Nose–Hoover
thermostat, and/or rigid water models could lead to pathological sampling
of the solutes’ conformation. In the extreme example of a methanol
molecule in aqueous solution, improper and sluggish setups could generate
two peaks in the distribution of the O–H bond length. We discuss
the factors responsible for this somewhat unexpected result and evoke
a simple and ancient technical fix-up to resolve this problem
Palladacycle-Catalyzed Deacetonative Sonogashira Coupling of Aryl Propargyl Alcohols with Aryl Chlorides
An efficient and
general protocol for the deacetonative Sonogashira
coupling of aryl propargyl alcohols with aryl chlorides is described.
The reaction proceeded smoothly with the catalyst system of palladacycle/Xphos.
This result represents the first successful deacetonative Sonogashira
version for electron-poor, electron-neutral, and even inactive sterically
hindered electron-rich aryl chlorides
Supplementary document for Terahertz 3-D fast line-scanning imaging enabled by 3-D printed devices - 6803521.pdf
Some simulation results and photo
Computing p<i>K</i><sub>a</sub> Values with a Mixing Hamiltonian Quantum Mechanical/Molecular Mechanical Approach
Accurate
computation of the p<i>K</i><sub>a</sub> value
of a compound in solution is important but challenging. Here, a new
mixing quantum mechanical/molecular mechanical (QM/MM) Hamiltonian
method is developed to simulate the free-energy change associated
with the protonation/deprotonation processes in solution. The mixing
Hamiltonian method is designed for efficient quantum mechanical free-energy
simulations by alchemically varying the nuclear potential, i.e., the
nuclear charge of the transforming nucleus. In p<i>K</i><sub>a</sub> calculation, the charge on the proton is varied in fraction
between 0 and 1, corresponding to the fully deprotonated and protonated
states, respectively. Inspired by the mixing potential QM/MM free
energy simulation method developed previously [H. Hu and W. T. Yang, <i>J. Chem. Phys.</i> <b>2005</b>, <i>123</i>,
041102], this method succeeds many advantages of a large class of
λ-coupled free-energy simulation methods and the linear combination
of atomic potential approach. Theory and technique details of this
method, along with the calculation results of the p<i>K</i><sub>a</sub> of methanol and methanethiol molecules in aqueous solution,
are reported. The results show satisfactory agreement with the experimental
data
Results from generalized linear model analysis (Schizophrenia).
<p>Results from generalized linear model analysis (Schizophrenia).</p
PGMA-Based Cationic Nanoparticles with Polyhydric Iodine Units for Advanced Gene Vectors
It is crucial for
successful gene delivery to develop safe, effective,
and multifunctional polycations. Iodine-based small molecules are
widely used as contrast agents for CT imaging. Herein, a series of
star-like polyÂ(glycidyl methacrylate) (PGMA)-based cationic vectors
(II-PGEA/II) with abundant flanking polyhydric iodine units are prepared
for multifunctional gene delivery systems. The proposed II-PGEA/II
star vector is composed of one iohexol intermediate (II) core and
five ethanolamine (EA) and II-difunctionalized PGMA arms. The amphipathic
II-PGEA/II vectors readily self-assemble into well-defined cationic
nanoparticles, where massive hydroxyl groups can establish a hydration
shell to stabilize the nanoparticles. The II introduction improves
cell viabilities of polycations. Moreover, by controlling the suitable
amount of introduced II units, the resultant II-PGEA/II nanoparticles
can produce fairly good transfection performances in different cell
lines. Particularly, the II-PGEA/II nanoparticles induce much better
in vitro CT imaging abilities in tumor cells than iohexol (one commonly
used commercial CT contrast agent). The present design of amphipathic
PGMA-based nanoparticles with CT contrast agents would provide useful
information for the development of new multifunctional gene delivery
systems
Selective Synthesis of Multisubstituted Olefins Utilizing <i>gem</i>- and <i>vic</i>-Diborylated Vinylsilanes Prepared by Silylborylation of an Alkynylboronate and Diborylation of Alkynylsilanes
The synthesis of a series of <i>gem</i>- and <i>vic</i>-diborylated vinylsilanes was
accomplished via highly
selective transition-metal-catalyzed <i>syn</i>-dimetalation
to the alkynylmetal species. This protocol served as a general synthetic
method toward regio- and stereodefined multisubstituted olefins. The
key steps are the diastereoselective Suzuki–Miyaura cross-coupling
reactions of <i>gem</i>- and <i>vic</i>-diborylated
vinylsilanes, in which the two boron groups showed discrete reactivities
to afford diverse precursors of multisubstituted olefins
Raw cost and meta-analysis of direct medical costs.<sup>†</sup>
<p>Raw cost and meta-analysis of direct medical costs.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0147169#t005fn002" target="_blank"><sup>†</sup></a></p
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