Molecular modeling Dotaz Zobrazit nápovědu
elektronický časopis
- Konspekt
- Přírodní vědy. Matematické vědy
- NLK Obory
- biologie
- chemie, klinická chemie
- biochemie
- biologie
- NLK Publikační typ
- elektronické časopisy
Interdisciplinary applied mathematics
1st ed. xliii, 634 s., barev. il.
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biologie
elektronický časopis
- MeSH
- automatizované zpracování dat MeSH
- molekulární struktura MeSH
- počítačová grafika MeSH
- Publikační typ
- periodika MeSH
- Konspekt
- Přírodní vědy. Matematické vědy
- NLK Obory
- biomedicínské inženýrství
- biologie
2nd ed. XII, 228 s. : il.
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biochemie
sv.
- MeSH
- chemie fyzikální MeSH
- molekulární struktura MeSH
- Publikační typ
- periodika MeSH
- Konspekt
- Chemie. Mineralogické vědy
- NLK Obory
- chemie, klinická chemie
- biologie
A simple molecular modeling method for the characterization of polymeric drug carriers is presented. Six biodegradable polymers have been investigated as drug carriers using molecular simulations: l-polylactide, d-polylactide, chitosan, polyglycolic acid, polyethylene glycol and cellulose. Cyclosporine A has been chosen as a model drug substance. Classical molecular dynamics and docking calculations were employed to model and predict polymer-drug interactions. These interactions have been analyzed by non-bond interaction energy and interaction parameter calculated using Flory-Huggins theory. Flexibility of polymer chains has been characterized by the change of gyration radius along the molecular dynamics trajectory. The relationship between mixing energy, chain length and chain flexibility has been revealed for each polymer/drug system.
- MeSH
- cyklosporin chemie MeSH
- molekulární modely * MeSH
- nosiče léků chemie MeSH
- polymery chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
elektronický časopis
- Konspekt
- Přírodní vědy. Matematické vědy
- NLK Obory
- přírodní vědy
- NLK Publikační typ
- elektronické časopisy
502 s.
- MeSH
- toxikologie MeSH
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- toxikologie
Phenyl valerate (PV) is a substrate for measuring the PVase activity of neuropathy target esterase (NTE), a key molecular event of organophosphorus-induced delayed neuropathy. A protein with PVase activity in chicken (model for delayed neurotoxicity) was identified as butyrylcholinesterase (BChE). Purified human butyrylcholinesterase (hBChE) showed PVase activity with a similar sensitivity to inhibitors as its cholinesterase (ChE) activity. Further kinetic and theoretical molecular simulation studies were performed. The kinetics did not fit classic competition models among substrates. Partially mixed inhibition was the best-fitting model to acetylthiocholine (AtCh) interacting with PVase activity. ChE activity showed substrate activation, and non-competitive inhibition was the best-fitting model to PV interacting with the non-activated enzyme and partial non-competitive inhibition was the best fitted model for PV interacting with the activated enzyme by excess of AtCh. The kinetic results suggest that other sites could be involved in those activities. From the theoretical docking analysis, we deduced other more favorable sites for binding PV related with Asn289 residue, situated far from the catalytic site ("PV-site"). Both substrates acethylcholine (ACh) and PV presented similar docking values in both the PV-site and catalytic site pockets, which explained some of the observed substrate interactions. Molecular dynamic simulations based on the theoretical structure of crystallized hBChE were performed. Molecular modeling studies suggested that PV has a higher potential for non-competitive inhibition, being also able to inhibit the hydrolysis of ACh through interactions with the PV-site. Further theoretical studies also suggested that PV could yet be able to promote competitive inhibition. We concluded that the kinetic and theoretical studies did not fit the simple classic competition among substrates, but were compatible with the interaction with two different binding sites.
Structure and behavior of amphiphilogel nanoparticles as a drug carriers for cyclosporine A (CsA) have been studied by the molecular modeling using empirical force field. Five atomistic models of a gel-based emulsions (GEM) with various gel compositions have been investigated in order to find a system most similar to a sixth atomistic model of self-microemulsifying drug delivery system (SMEDDS) taken as an exemplar of CsA delivery system. Structural parameters and energy characteristics (i.e. non-bond interaction energy between CsA and whole remaining components of a gel nanoparticle, CsA/gel nanoparticle intermolecular non-bond interaction energy, CsA-gel molecule pair interaction energy, volume fraction, concentration profiles and number of pervaded water molecules) of these six models in a waterless form and in a water containing form have been studied in dependence on the composition. The Flory-Huggins theory as implemented in the Accelrys Materials Studio 4.2 modeling environment was used to study the pair interactions of cyclosporine A with various types of surfactants. Structural parameters and energy characteristics of all systems have been compared and one composition was selected as a very promising for further experimental study.
- MeSH
- aplikace orální MeSH
- cyklosporin aplikace a dávkování chemie MeSH
- emulze MeSH
- gely MeSH
- imunosupresiva aplikace a dávkování chemie MeSH
- molekulární modely MeSH
- nanočástice MeSH
- povrchově aktivní látky chemie MeSH
- systémy cílené aplikace léků MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
