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Allosteric Interactions with Muscarinic Acetylcholine Receptors: Complex Role of the Conserved Tryptophan M2422Trp in a Critical Cluster of Amino Acids for Baseline Affinity, Subtype Selectivity, and
M2422Trp and the spatially adjacent M2177Tyr, as well as M2423Thr, form a cluster of amino acids within the allosteric binding cleft that is pivotal for both M2/M5 subtype selectivity and baseline affinity ofallosteric agents. Expand
Molecular design of two sterol 14α-demethylase homology models and their interactions with the azole antifungals ketoconazole and bifonazole
It is possible to explain the enantioselectivity of the human enzyme and also to predict the binding mode of the isomers of ketoconazole in the active site of the fungal model. Expand
Molecular Modeling, Basic Principles and Applications
In a clear and concise manner, the title leads the reader from simple modeling calculations for small molecules to the complex modeling systems used to simulate protein and other relevant biomolecules. Expand
Atypical Muscarinic Allosteric Modulation: Cooperativity between Modulators and Their Atypical Binding Topology in Muscarinic M2 and M2/M5 Chimeric Receptors
The atypical actions of tacrine and Duo3 involve different modes of receptor interaction, but their sites of attachment seem to be the “common” allosteric binding domain at the entrance to the orthosteric ligand binding pocket of the M2-receptor. Expand
Molecular model of an alpha-helical prion protein dimer and its monomeric subunits as derived from chemical cross-linking and molecular modeling calculations.
Molecular dynamics of the structure after release of the constraint indicated an intrinsic stability of the domain of amino acids 90-124, showing the N-terminal amino acids (90-124) are not as flexible as known from NMR analysis. Expand
N-(ω-(4-(2-Methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as Dopamine D2 and D3 Receptor Ligands
The dopamine D3 receptor is recognized as a potential therapeutic target for the treatment of various neurological and psychiatric disorders. Targetting high affinity and D3 versus D2Expand
Key determinants of nucleotide-activated G protein-coupled P2Y(2) receptor function revealed by chemical and pharmacological experiments, mutagenesis and homology modeling.
The P2Y(2) receptor, which is activated by UTP, ATP, and dinucleotides, was studied as a prototypical nucleotide-activated GPCR and R272 (extracellular loop EL3) was found to play a gatekeeper role, presumably responsible for recognition and orientation of the nucleotides. Expand
Mechanisms of antibiotic resistance: QM/MM modeling of the acylation reaction of a class A beta-lactamase with benzylpenicillin.
This work modeled the complete mechanism of acylation with benzylpenicillin, using a combined quantum mechanical and molecular mechanical (QM/MM) method, and demonstrates the importance of the "oxyanion hole" in stabilizing the transition state and the tetrahedral intermediate. Expand
Allosteric site on muscarinic acetylcholine receptors: identification of two amino acids in the muscarinic M2 receptor that account entirely for the M2/M5 subtype selectivities of some structurally
Two amino acids account entirely for the (approximately 100-fold) M2/M5 selectivity of the alkane-bisammonium and the caracurine V type allosteric ligands at NMS-free M2 receptors. Expand
Alpha-lipoic acid as a directly binding activator of the insulin receptor: protection from hepatocyte apoptosis.
Computer modeling studies revealed a direct binding site for alpha-lipoic acid at the tyrosine kinase domain of the insulin receptor, suggesting a stabilizing function in loop A that is involved in ATP binding, which might make alpha- Lipoic Acid a model substance for the development of insulin mimetics. Expand