elektronický časopis
- Conspectus
- Přírodní vědy. Matematické vědy
- NML Fields
- biologie
- chemie, klinická chemie
- biochemie
- biologie
- NML Publication type
- elektronické časopisy
Interdisciplinary applied mathematics
1st ed. xliii, 634 s., barev. il.
61 stran : ilustrace ; 21 cm
- MeSH
- Immune Tolerance physiology MeSH
- Molecular Biology MeSH
- Publication type
- Congress MeSH
- Collected Work MeSH
- Conspectus
- Biochemie. Molekulární biologie. Biofyzika
- NML Fields
- biologie
- alergologie a imunologie
2nd ed. XII, 228 s. : il.
The advent of cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), coupled with computational modeling, has enabled the creation of integrative 3D models of viruses, bacteria, and cellular organelles. These models, composed of thousands of macromolecules and billions of atoms, have historically posed significant challenges for manipulation and visualization without specialized molecular graphics tools and hardware. With the recent advancements in GPU rendering power and web browser capabilities, it is now feasible to render interactively large molecular scenes directly on the web. In this work, we introduce Mesoscale Explorer, a web application built using the Mol* framework, dedicated to the visualization of large-scale molecular models ranging from viruses to cell organelles. Mesoscale Explorer provides unprecedented access and insight into the molecular fabric of life, enhancing perception, streamlining exploration, and simplifying visualization of diverse data types, showcasing the intricate details of these models with unparalleled clarity.
- MeSH
- Cryoelectron Microscopy * methods MeSH
- Models, Molecular * MeSH
- Software * MeSH
- Viruses chemistry ultrastructure MeSH
- Publication type
- Journal Article MeSH
elektronický časopis
- MeSH
- Electronic Data Processing MeSH
- Molecular Structure MeSH
- Computer Graphics MeSH
- Publication type
- Periodical MeSH
- Conspectus
- Přírodní vědy. Matematické vědy
- NML Fields
- biomedicínské inženýrství
- 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.
Tato práce podává přehled o preklinických modelech agresivity a jejich validitě včetně dosavadních možností experimentální terapie. Zatímco u ostatních psychických onemocnění je poměrně těžké najít odpovídající model splňující kritéria validity, agresivitu, jako velmi starý etologický prvek, můžeme modelovat poměrně snadno. Avšak poměrně dobré modely agresivity, které můžeme používat, nezaručují snadný vývoj specifických antiagresivních léčiv. Léčba agresivity je zatím spojena převážně s celkovým útlumem organizmu či přinejmenším kvalitativní změnou i ostatních druhů chování. Vzhledem k dùležitosti agresivního chování pro přežití jedince i celého druhu bude tento fenomén pravdìpodobně regulován více mechanizmy, a proto i jeho ovlivnění asi nebude záležitostí jednoho receptorového systému, a proto modelování, neurobiologie či léèča agresivity je stále předmětem dalšího výzkumu.
This review summarizes preclinical models of aggression including their validity and possibilities of experimental treatment. W hile other psychiatric disease is very hard to construct, the aggression, as a very old ethological element, is relatively easy to s imulate. However, good models of aggression do not guarantee an easy development of drugs with antiaggressive properties. The treatment of aggres sion is often connected with sedation and changes of other behavioral elements. With regard to importance of aggression for survival of an individual and species, control of aggression is probably not influenced by only one neurotransmitter system. That is why model ing, neurobiology and treatment of aggression is still a matter of further research.
sv.
- MeSH
- Chemistry, Physical MeSH
- Molecular Structure MeSH
- Publication type
- Periodical MeSH
- Conspectus
- Chemie. Mineralogické vědy
- NML Fields
- chemie, klinická chemie
- biologie
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.
