Partial atomic charges serve as a simple model for the electrostatic distribution of a molecule that drives its interactions with its surroundings. Since partial atomic charges are frequently used in computational chemistry, chemoinformatics and bioinformatics, many computational approaches for calculating them have been introduced. The most applicable are fast and reasonably accurate empirical charge calculation approaches. Here, we introduce Atomic Charge Calculator II (ACC II), a web application that enables the calculation of partial atomic charges via all the main empirical approaches and for all types of molecules. ACC II implements 17 empirical charge calculation methods, including the highly cited (QEq, EEM), the recently published (EQeq, EQeq+C), and the old but still often used (PEOE). ACC II enables the fast calculation of charges even for large macromolecular structures. The web server also offers charge visualization, courtesy of the powerful LiteMol viewer. The calculation setup of ACC II is very straightforward and enables the quick calculation of high-quality partial charges. The application is available at https://acc2.ncbr.muni.cz.

• MeSH
• fenoly chemie   MeSH
• internet MeSH
• molekulární modely * MeSH
• molekulární struktura MeSH
• nikotinové receptory chemie   MeSH
• protein X asociovaný s bcl-2 chemie   MeSH
• software * MeSH
• statická elektřina MeSH
• vodík chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fenoly MeSH
• nikotinové receptory MeSH
• protein X asociovaný s bcl-2 MeSH
• vodík MeSH

The role of negatively charged amino acids in the F-loop of the beta 4 subunit in channel activation and desensitization was studied using the patch-clamp technique. The selected amino acids were changed to their neutral analogs via point mutations. Whole-cell currents were recorded in COS cells transiently transfected with the alpha 3 beta 4 nicotinic acetylcholine receptor. The application of acetylcholine (ACh), nicotine (Nic), cytisine (Cyt), carbamylcholine (CCh) and epibatidine (Epi) to cells clamped at -40 mV produced inward currents which displayed biphasic desensitization. The EC50 of Epi and Nic were increased by a factor of 3-6 due to mutations D191N or D192N. Only Epi remained an agonist in the double-mutated receptors with EC50 increased 17-fold. The interaction of the receptors with the competitive antagonist (+)tubocurarine (TC) was weakened almost 3-fold in the double-mutated receptors. The mutations increased the proportion of the slower desensitization component and increased the response plateau, resulting in decreased receptor desensitization. The double mutation substantially accelerated the return from long-term desensitization induced by Epi.

• MeSH
• aminokyseliny chemie   metabolismus   MeSH
• bicyklické sloučeniny heterocyklické farmakologie   MeSH
• Cercopithecus aethiops MeSH
• COS buňky MeSH
• kinetika MeSH
• krysa rodu Rattus MeSH
• molekulární sekvence - údaje MeSH
• mutace genetika   MeSH
• neurony metabolismus   MeSH
• nikotin farmakologie   MeSH
• nikotinové receptory chemie   metabolismus   MeSH
• nikotinoví agonisté farmakologie   MeSH
• podjednotky proteinů chemie   metabolismus   MeSH
• pyridiny farmakologie   MeSH
• sekundární struktura proteinů MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• tubokurarin farmakologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• bicyklické sloučeniny heterocyklické MeSH
• epibatidine MeSH Prohlížeč
• nikotin MeSH
• nikotinové receptory MeSH
• nikotinoví agonisté MeSH
• podjednotky proteinů MeSH
• pyridiny MeSH
• tubokurarin MeSH

Adult and embryonic nicotinic receptors expressed in COS cells have similar affinities for acetylcholine but differ in their Hill coefficient. Parameters of wild-type receptors were compared with those of receptors with mutated delta and gamma subunits in selected negatively charged amino acids, which were expected to participate in agonist binding. A tentative scheme of affinities, allosteric interactions and channel gating efficacy was used for assessing the role of mutated amino acids in the channel function. In three models, the parameters of wild-type embryonic and adult receptors were compared with those of receptors with mutated delta and gamma subunits. The analysis of different models of channel activation indicates that negatively charged amino acids which were mutated in the delta subunit in embryonic receptors participate in channel gating and in allosteric interactions between subunits rather than directly in agonist binding. Changes in the gamma subunit in the embryonic receptors and delta subunit in the adult receptors could equally affect agonist binding, allosteric coupling between subunits or channel gating.

• MeSH
• acetylcholin metabolismus   MeSH
• bodová mutace MeSH
• chemické modely MeSH
• COS buňky MeSH
• genetické vektory MeSH
• klonování DNA MeSH
• kosterní svaly embryologie   metabolismus   MeSH
• myši MeSH
• nikotinové receptory biosyntéza   chemie   metabolismus   MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• srovnávací studie MeSH
• Názvy látek
• acetylcholin MeSH
• nikotinové receptory MeSH

The existence of dihydropyridine receptor in crayfish striated muscle was proved by Northern blot analysis and 3H PN 200--110 binding. The alpha 1 subunit is encoded by a 8300 nt mRNA population and is expressed as 190 kD protein in crayfish T-tubular system, which binds 3H PN 200--110 (Bmax 1.5 +/- 0.4 pmol/mg protein and KD 6.2 +/- 0.8 nmol/l). The purified protein is phosphorylated by cAMP-dependent protein kinase. The dihydropyridine receptor in crayfish striated muscle also contains alpha 2 subunit, which on Northern blot gives the same signal as the alpha 2 subunit from rabbit skeletal muscle.

• MeSH
• blokátory kalciových kanálů metabolismus   MeSH
• exprese genu MeSH
• konformace proteinů MeSH
• messenger RNA genetika   MeSH
• molekulová hmotnost MeSH
• nikotinové receptory chemie   genetika   metabolismus   MeSH
• severní raci metabolismus   MeSH
• svaly metabolismus   MeSH
• vápníkové kanály MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• blokátory kalciových kanálů MeSH
• messenger RNA MeSH
• nikotinové receptory MeSH
• vápníkové kanály MeSH