1,783 research outputs found
A Follow-up Study of Industrial Technology Graduates of Old Dominion University 1987-1995
Through the follow-up study, data was compiled toward answering the following questions: 1. What was the current employment status of the Industrial Technology graduates? 2. What types of employment have been held by the Industrial Technology graduates? 3. What was the typical salary for the Industrial Technology graduates? 4. What were the recommendations of the graduates for Industrial Technology program improvements
Simple estimation of absolute free energies for biomolecules
One reason that free energy difference calculations are notoriously difficult
in molecular systems is due to insufficient conformational overlap, or
similarity, between the two states or systems of interest. The degree of
overlap is irrelevant, however, if the absolute free energy of each state can
be computed. We present a method for calculating the absolute free energy that
employs a simple construction of an exactly computable reference system which
possesses high overlap with the state of interest. The approach requires only a
physical ensemble of conformations generated via simulation, and an auxiliary
calculation of approximately equal central-processing-unit (CPU) cost.
Moreover, the calculations can converge to the correct free energy value even
when the physical ensemble is incomplete or improperly distributed. As a "proof
of principle," we use the approach to correctly predict free energies for test
systems where the absolute values can be calculated exactly, and also to
predict the conformational equilibrium for leucine dipeptide in implicit
solvent.Comment: To appear in J. Chem. Phys., 10 pages, 6 figure
Coupling hydrophobic, dispersion, and electrostatic contributions in continuum solvent models
Recent studies of the hydration of micro- and nanoscale solutes have
demonstrated a strong {\it coupling} between hydrophobic, dispersion and
electrostatic contributions, a fact not accounted for in current implicit
solvent models. We present a theoretical formalism which accounts for coupling
by minimizing the Gibbs free energy with respect to a solvent volume exclusion
function. The solvent accessible surface is output of our theory. Our method is
illustrated with the hydration of alkane-assembled solutes on different length
scales, and captures the strong sensitivity to the particular form of the
solute-solvent interactions in agreement with recent computer simulations.Comment: 11 pages, 2 figure
Enhanced conformational space sampling improves the prediction of chemical shifts in proteins.
A biased-potential molecular dynamics simulation method, accelerated molecular dynamics (AMD), was combined with the chemical shift prediction algorithm SHIFTX to calculate (1)H(N), (15)N, (13)Calpha, (13)Cbeta, and (13)C' chemical shifts of the ankyrin repeat protein IkappaBalpha (residues 67-206), the primary inhibitor of nuclear factor kappa-B (NF-kappaB). Free-energy-weighted molecular ensembles were generated over a range of acceleration levels, affording systematic enhancement of the conformational space sampling of the protein. We have found that the predicted chemical shifts, particularly for the (15)N, (13)Calpha, and (13)Cbeta nuclei, improve substantially with enhanced conformational space sampling up to an optimal acceleration level. Significant improvement in the predicted chemical shift data coincides with those regions of the protein that exhibit backbone dynamics on longer time scales. Interestingly, the optimal acceleration level for reproduction of the chemical shift data has previously been shown to best reproduce the experimental residual dipolar coupling (RDC) data for this system, as both chemical shift data and RDCs report on an ensemble and time average in the millisecond range
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Substrate concentration dependence of the diffusion-controlled steady-state rate constant
The Smoluchowski approach to diffusion-controlled reactions is generalized to
interacting substrate particles by including the osmotic pressure and
hydrodynamic interactions of the nonideal particles in the Smoluchoswki
equation within a local-density approximation. By solving the strictly
linearized equation for the time-independent case with absorbing boundary
conditions, we present an analytic expression for the diffusion-limited
steady-state rate constant for small substrate concentrations in terms of an
effective second virial coefficient B_2*. Comparisons to Brownian dynamics
simulations excluding HI show excellent agreement up to bulk number densities
of B_2* rho_0 < 0.4 for hard sphere and repulsive Yukawa-like interactions
between the substrates. Our study provides an alternative way to determine the
second virial coefficient of interacting macromolecules experimentally by
measuring their steady-state rate constant in diffusion-controlled reactions at
low densities.Comment: 7 pages, 3 figure
Contribution of Unresolved Point Sources to the Diffuse X-ray Background below 1 keV
We present here the analysis of X-rays point sources detected in several
observations available in the XMM-Newton public archive. We focused, in
particular, on energies below 1 keV, which are of particular relevance to the
understanding of the Diffuse X-ray Background. The average field of all the
exposures is 0.09 deg^-2. We reached an average flux sensitivity of 5.8x10^-16
erg s^-1 cm^-2 in the soft band (0.5-2.0 keV) and 2.5x10^-16 erg s^-1 cm^-2 in
the very soft band (0.4-0.6 keV). In this paper we discuss the logN-logS
results, the contribution to the integrated X-ray sky flux, and the properties
of the cumulative spectrum from all sources. In particular, we found an excess
flux at around 0.5 keV in the composite spectrum of faint sources. The excess
seems to be a general property of all the fields observed suggesting an
additional class of weak sources is contributing to the X-ray emission at these
energies. Combining our results with previous investigations we have also
quantified the contribution of the individual components of the diffuse X-ray
Background in the 3/4 keV band.Comment: Accepted for publication in ApJ; 27 pages, 8 figure
Functional dynamics of the folded ankyrin repeats of I kappa B alpha revealed by nuclear magnetic resonance.
Inhibition of nuclear factor kappaB (NF-kappaB) is mainly accomplished by IkappaB alpha, which consists of a signal response sequence at the N-terminus, a six-ankyrin repeat domain (ARD) that binds NF-kappaB, and a C-terminal PEST sequence. Previous studies with the ARD revealed that the fifth and sixth repeats are only partially folded in the absence of NF-kappaB. Here we report NMR studies of a truncated version of IkappaB alpha, containing only the first four ankyrin repeats, IkappaB alpha(67-206). This four-repeat segment is well-structured in the free state, enabling full resonance assignments to be made. H-D exchange, backbone dynamics, and residual dipolar coupling (RDC) experiments reveal regions of flexibility. In addition, regions consistent with the presence of micro- to millisecond motions occur periodically throughout the repeat structure. Comparison of the RDCs with the crystal structure gave only moderate agreement, but an ensemble of structures generated by accelerated molecular dynamics gave much better agreement with the measured RDCs. The regions showing flexibility correspond to those implicated in entropic compensation for the loss of flexibility in ankyrin repeats 5 and 6 upon binding to NF-kappaB. The regions showing micro- to millisecond motions in the free protein are the ends of the beta-hairpins that directly interact with NF-kappaB in the complex
Non-bisphosphonate inhibitors of isoprenoid biosynthesis identified via computer-aided drug design.
The relaxed complex scheme, a virtual-screening methodology that accounts for protein receptor flexibility, was used to identify a low-micromolar, non-bisphosphonate inhibitor of farnesyl diphosphate synthase. Serendipitously, we also found that several predicted farnesyl diphosphate synthase inhibitors were low-micromolar inhibitors of undecaprenyl diphosphate synthase. These results are of interest because farnesyl diphosphate synthase inhibitors are being pursued as both anti-infective and anticancer agents, and undecaprenyl diphosphate synthase inhibitors are antibacterial drug leads
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