1,429 research outputs found
Will it gel? Successful computational prediction of peptide gelators using physicochemical properties and molecular fingerprints
The self-assembly of low molecular weight gelators to form gels has enormous potential for cell culturing, optoelectronics, sensing, and for the preparation of structured materials. There is an enormous “chemical space” of gelators. Even within one class, functionalised dipeptides, there are many structures based on both natural and unnatural amino acids that can be proposed and there is a need for methods that can successfully predict the gelation propensity of such molecules. We have successfully developed computational models, based on experimental data, which are robust and are able to identify in silico dipeptide structures that can form gels. A virtual computational screen of 2025 dipeptide candidates identified 9 dipeptides that were synthesised and tested. Every one of the 9 dipeptides synthesised and tested were correctly predicted for their gelation properties. This approach and set of tools enables the “dipeptide space” to be searched effectively and efficiently in order to deliver novel gelator molecules
Ringing the eigenmodes from compact manifolds
We present a method for finding the eigenmodes of the Laplace operator acting
on any compact manifold. The procedure can be used to simulate cosmic microwave
background fluctuations in multi-connected cosmological models. Other
applications include studies of chaotic mixing and quantum chaos.Comment: 11 pages, 8 figures, IOP format. To be published in the proceedings
of the Cleveland Cosmology and Topology Workshop 17-19 Oct 1997. Submitted to
Class. Quant. Gra
Sidechain control of porosity closure in multiple peptide-based porous materials by cooperative folding
Porous materials find application in separation, storage and catalysis. We report a crystalline porous solid formed by coordination of metal centres with a glycylserine dipeptide. We prove experimentally that the structure evolves from a solvated porous into a non-porous state as result of ordered displacive and conformational changes of the peptide that suppress the void space in response to environmental pressure. This cooperative closure, which recalls the folding of proteins, retains order in three-dimensions and is driven by the hydroxyl groups acting as H-bond donors in the peptide sequence through the serine residue. This ordered closure is also displayed by multipeptide solid solutions in which the combination of different sequences of amino acids controls their guest response in a non-linear way. This functional control can be compared to the effect of single point mutations in proteins, where the exchange of single amino acids can radically alter structure and functio
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Texas Field Experiment Results: Performance of the Weatherization Assistance Program in Hot-Climate, Low-Income Homes
A field test involving 35 houses was performed in Texas between 2000 and 2003 to study the response of low-income homes in hot climates to weatherization performed as part of the U.S Department of Energy Weatherization Assistance Program and to investigate certain methods to improve weatherization performance. The study found that improved Program designs and the use of advanced energy audits resulted in better weatherization measures being installed (use of blower doors to guide the infiltration work, more frequent installation of attic insulation, and installation of wall insulation) in the study homes, improved space-heating savings performance compared to the Program as implemented in the hot climates in 1989, and more comfortable indoor temperatures. Two key policy dilemmas for Texas and other hot-climate states were highlighted by the study; namely, how to balance expenditures between installing cost-effective weatherization measures and performing health, safety, and repair items, and that health, safety, and repair items can have an adverse impact on energy savings, which further complicates the weatherization decision process. Several occupant and equipment-related behaviors were observed in the field test homes that help explain why audits may over predict energy consumptions and savings and why air-conditioning electricity savings are difficult to measure. Based on this study, it is recommended that states in hot climates be encouraged to select from an expanded list of measures using advanced audits or other techniques, and further studies examining the benefits obtained from air conditioner measures should be performed. In addition, guidelines should be developed for the hot-climate states on how to (a) balance the objectives of saving energy, improving health and safety, and addressing repair issues, and (b) select repair items
Structure-based design of nucleoside-derived analogues as sulfotransferase inhibitors
Sulfotransferases (STs) catalyse the transfer of a sulfonyl group (‘sulfation’) from the enzyme co-factor 3ʹ-phosphoadenosine 5ʹ-phosphosulfate (PAPS) to a variety of biomolecules. Tyrosine sulfation of proteins and carbohydrate sulfation play a crucial role in many protein-protein interactions and cell signalling pathways in the extracellular matrix. This is catalysed by several membrane-bound STs, including tyrosylprotein sulfotransferase 1 (TPST1) and heparan sulfate 2-O-sulfotransferase (HS2ST1). Recently, involvement of these enzymes and their post-translational modifications in a growing number of disease areas has been reported, including inflammation, cancer and Alzheimer’s disease. Despite their growing importance, the development of small molecules to probe the biological effect of TPST and carbohydrate ST inhibition remains in its infancy. We have used a structure-based approach and molecular docking to design a library of adenosine 3',5'-diphosphate (PAP) and PAPS mimetics based upon 2'-deoxyadenosine and using 2'-deoxy-PAP as a benchmark. The use of allyl groups as masked methyl esters was exploited in the synthesis of PAP-mimetics, and click chemistry was employed for the divergent synthesis of a series of PAPS-mimetics. A suite of in vitro assays employing TPST1 and HS2ST, and a kinase counter screen, were used to evaluate inhibitory parameters and relative specificity for the STs
Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus
Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza. Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC50s in the range of 0.14–5.0 μM. Additionally a quantitative structure–property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set. Conclusion: A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified
In Situ Surface-Enhanced Infrared Spectroscopy to Identify Oxygen Reduction Products in Nonaqueous Metal-Oxygen Batteries
We
report on the detection of metastable, solvated, and surface adsorbed
alkali metal–oxygen (M–O<sub>2</sub>) discharge species
using in situ attenuated total reflectance surface enhanced infrared
absorption spectroscopy (ATR-SEIRAS). Oxygen–oxygen stretching
bands (ν<sub>O–O</sub>) of superoxide species formed
during M–O<sub>2</sub> battery discharge have been challenging
to observe by conventional infrared (IR) techniques, and because of
this, there has been limited use of IR techniques for in situ monitoring
of the discharge products at the cathode in metal–O<sub>2</sub> batteries. We explore SEIRAS technique to investigate lithium–oxygen
and sodium–oxygen electrochemistry in acetonitrile (MeCN; a
low Gutmann donor number solvent) as well as dimethyl sulfoxide (DMSO;
a high Gutmann donor number solvent) in order to demonstrate the feasibility
of our approach in the ongoing efforts toward the realization of M–O<sub>2</sub> battery technology. In situ IR spectroscopy studies, together
with a coupled-cluster method including perturbative triple excitations
[CCSD(T)] calculations, establishes that certain M–O and O–O
stretching bands (ν<sub>M–O</sub> and ν<sub>O–O</sub>) of metal superoxide and peroxide molecular species are IR active,
although these vibrational modes are silent or suppressed in their
crystalline forms. An in situ IR spectroscopy based approach to distinguish
between “solution mediated” and “surface confined”
discharge pathways in nonaqueous M–O<sub>2</sub> batteries
is demonstrated
Conformational control of structure and guest uptake by a tripeptide-based porous material
Chemical processes often rely on the selective sorting and transformation of molecules according to their size, shape and chemical functionality. For example, porous materials such as zeolites achieve the required selectivity through the constrained pore dimensions of a single structure.1 In contrast, proteins function by navigating between multiple metastable structures using bond rotations of the polypeptide,2,3 where each structure lies in one of the minima of a conformational energy landscape and can be selected according to the chemistry of the molecules interacting with the protein.3 Here we show that rotation about covalent bonds in a peptide linker can change a flexible metal-organic framework (MOF) to afford nine distinct crystal structures, revealing a conformational energy landscape characterised by multiple structural minima. The uptake of small molecule guests by the MOF can be chemically triggered by inducing peptide conformational change. This change transforms the material from a minimum on the landscape that is inactive for guest sorption to an active one. Chemical control of the conformation of a flexible organic linker offers a route to modify the pore geometry and internal surface chemistry and thus the function of open-framework materials
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