Soft glucocorticoids are compounds that are biotransformed to inactive and non-toxic metabolites and have fewer side effects than traditional glucocorticoids. A new class of 17β-carboxamide steroids has been recently introduced by our group. In this study, local anti-inflammatory activity of these derivatives was evaluated by use of the croton oil-induced ear edema test. Glucocorticoids with the highest maximal edema inhibition (MEI) were pointed out, and the systemic side effects of those with the lowest EC50 values were significantly lower in comparison to dexamethasone. A 3D-QSAR model was created and employed for the design of 27 compounds. By use of the sequential combination of ligand-based and structure-based virtual screening, three compounds were selected from the ChEMBL library and used as a starting point for the design of 15 derivatives. Molecular docking analysis of the designed derivatives with the highest predicted MEI and relative glucocorticoid receptor binding affinity (20, 22, 24-1, 25-1, 27, VS7, VS13, and VS14) confirmed the presence of interactions with the glucocorticoid receptor that are important for the activity.

• Klíčová slova
• Anti-inflammatory activity, QSAR, Rational drug design,
• MeSH
• antiflogistika škodlivé účinky   chemie   farmakologie   MeSH
• design s pomocí počítače * MeSH
• edém chemicky indukované   farmakoterapie   MeSH
• glukokortikoidy škodlivé účinky   chemie   farmakologie   MeSH
• krotonový olej MeSH
• krysa rodu Rattus MeSH
• kvantitativní vztahy mezi strukturou a aktivitou MeSH
• molekulární konformace MeSH
• nemoci ucha chemicky indukované   farmakoterapie   MeSH
• potkani Wistar MeSH
• racionální návrh léčiv MeSH
• simulace molekulového dockingu MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• glukokortikoidy MeSH
• krotonový olej MeSH

• MeSH
• design s pomocí počítače * MeSH
• genetické inženýrství * MeSH
• krystalografie rentgenová * MeSH
• racionální návrh léčiv * MeSH
• Publikační typ
• časopisecké články MeSH
• souhrny MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

The semiempirical quantum mechanical (SQM) methods used in drug design are commonly parametrized and tested on data sets of systems that may not be representative models for drug-biomolecule interactions in terms of both size and chemical composition. This is addressed here with a new benchmark data set, PLF547, derived from protein-ligand complexes, consisting of complexes of ligands with protein fragments (such as amino-acid side chains), with interaction energies based on MP2-F12 and DLPNO-CCSD(T) calculations. From these, composite benchmark interaction energies are also built for complexes of the ligand with the complete active site of the protein (PLA15 data set). These data sets are used to test multiple SQM methods with corrections for noncovalent interactions; the role of the solvation model in the calculations is tested as well.

• MeSH
• kvantová teorie * MeSH
• léčivé přípravky * MeSH
• ligandy MeSH
• racionální návrh léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• léčivé přípravky * MeSH
• ligandy MeSH

• Klíčová slova
• airway management, cleft lip, cleft palate, complications, difficult airway, protective obturator,
• MeSH
• 3D tisk MeSH
• design s pomocí počítače MeSH
• dítě MeSH
• lidé MeSH
• pilotní projekty MeSH
• rozštěp patra * MeSH
• rozštěp rtu * MeSH
• zajištění dýchacích cest MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• dopisy MeSH

The separation process in capillary micellar electrochromatography (MEKC) can be modelled using artificial neural networks (ANNs) and optimisation of MEKC methods can be facilitated by combining ANNs with experimental design. ANNs have shown attractive possibilities for non-linear modelling of response surfaces in MEKC and it was demonstrated that by combining ANN modelling with experimental design, the number of experiments necessary to search and find optimal separation conditions can be reduced significantly. A new general approach for computer-aided optimisation in MEKC has been proposed which, because of its general validity, can also be applied in other separation techniques.

• MeSH
• chromatografie micelární elektrokinetická kapilární metody   MeSH
• EDTA analogy a deriváty   chemie   MeSH
• kovy analýza   MeSH
• neuronové sítě * MeSH
• počítačová simulace MeSH
• výzkumný projekt MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CDTA MeSH Prohlížeč
• EDTA MeSH
• kovy MeSH

This study focuses on the drop foot case related to hyperthyroidism of the ankle joint resulting in the relaxation of the toes during walking. This condition requires treatment using an ankle-foot orthosis. Traditional orthosis techniques lack precision and depend on the skill of the fabricator. This research aims to make a bias in ankle-foot orthosis design and analysis methods, where a complete methodology of numerical design and testing has been proposed using advanced engineering software. A numerical model of the patient's foot was generated and used to design an ankle-foot orthosis model using SolidWorks. The designed model was mechanically analyzed by the finite element method using ANSYS Workbench 16.1 under different static and dynamic loading conditions. The ankle-foot orthosis model was numerically designed and analyzed before the manufacturing process. This is believed to reduce time and material loss and foster the use of numerical models in biomedical applications. This study suggests focusing on the design and analysis of orthoses according to the patient's measurements. This is expected to increase the comfort and raise the level of treatment. Numerical design methods also enable precise manufacturing using computerized devices such as three-dimensional printers.

• Klíčová slova
• Drop foot, ankle–foot orthosis, energy dissipation, finite element analysis, rotational hardness,
• MeSH
• analýza metodou konečných prvků MeSH
• biomechanika MeSH
• chůze fyziologie   MeSH
• design s pomocí počítače MeSH
• design vybavení metody   MeSH
• hlezenní kloub fyziologie   MeSH
• lidé MeSH
• neurologické poruchy chůze * etiologie   patofyziologie   terapie   MeSH
• ortézy nohy (od hlezna dolů) * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The application of the pharmacophore concept to design new drugs is discussed. The focus is on the application of computer-assisted drug design methods (CADD) in the discovery of new leads.

• MeSH
• databáze jako téma MeSH
• design s pomocí počítače MeSH
• molekulární konformace MeSH
• racionální návrh léčiv * MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH

A fully-vectorial mode solver based on the finite element method is employed in a combination with the downhill simplex method the dispersion optimization of photonic crystal fibers made from highly nonlinear glasses. The nonlinear fibers are designed for telecom applications such as parametric amplification, wavelength conversion, ultra-fast switching and regeneration of optical signals. The optimization is carried in terms of the zero dispersion wavelength, dispersion magnitude and nonlinear coefficient and confinement loss in the wavelength range around 1.55 microm. We restrict our work to the index-guiding fiber structures a small number of hexagonally arrayed air holes.

• MeSH
• analýza selhání vybavení MeSH
• design s pomocí počítače * MeSH
• design vybavení MeSH
• fotony MeSH
• nelineární dynamika MeSH
• optická vlákna * MeSH
• počítačová simulace MeSH
• radiační rozptyl MeSH
• refraktometrie přístrojové vybavení   MeSH
• sklo chemie   MeSH
• světlo MeSH
• telekomunikace přístrojové vybavení   MeSH
• teoretické modely * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A microfabricated pneumatic electrospray nebulizer has been developed and evaluated using computer simulations and experimental measurements of the MS signals. The microdevice under development is designed for electrospray MS interfacing without the need to fabricate an electrospray needle and can be used as a disposable or an integral part of a reusable system. The design of the chip layout was supported by computational fluid dynamics simulations. The tested microdevices were fabricated in glass using conventional photolithography, followed by wet chemical etching and thermal bonding. The performance of the microfabricated nebulizer was evaluated by means of TOF-MS with a peptide mixture. It was demonstrated that the nebulizer, operating at supersonic speed of the nebulizing gas, produced very stable nanospray (900 nL/min) as documented by less than 0.1% (SE) fluctuation in total mass spectrometric signal intensity.

• Klíčová slova
• CFD, Electrospray, Microfabrication, Modeling, Nebulizer,
• MeSH
• design s pomocí počítače * MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací metody   MeSH
• mikrofluidní analytické techniky přístrojové vybavení   MeSH
• nebulizátory a vaporizátory * MeSH
• počítačová simulace * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

By binding to the spliceosomal protein Snu66, the human ubiquitin-like protein Hub1 is a modulator of the spliceosome performance and facilitates alternative splicing. Small molecules that bind to Hub1 would be of interest to study the protein-protein interaction of Hub1/Snu66, which is linked to several human pathologies, such as hypercholesterolemia, premature aging, neurodegenerative diseases, and cancer. To identify small molecule ligands for Hub1, we used the interface analysis, peptide modeling of the Hub1/Snu66 interaction and the fragment-based NMR screening. Fragment-based NMR screening has not proven sufficient to unambiguously search for fragments that bind to the Hub1 protein. This was because the Snu66 binding pocket of Hub1 is occupied by pH-sensitive residues, making it difficult to distinguish between pH-induced NMR shifts and actual binding events. The NMR analyses were therefore verified experimentally by microscale thermophoresis and by NMR pH titration experiments. Our study found two small peptides that showed binding to Hub1. These peptides are the first small-molecule ligands reported to interact with the Hub1 protein.

• Klíčová slova
• anti-cancer therapy, nuclear magnetic resonance, protein-peptide docking, protein-protein interactions, small-molecule inhibitors,
• MeSH
• alternativní sestřih * MeSH
• lidé MeSH
• ligandy MeSH
• magnetická rezonanční spektroskopie MeSH
• počítače MeSH
• spliceozomy * metabolismus   MeSH
• ubikvitiny genetika   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ligandy MeSH
• ubikvitiny MeSH