Strain-Dependent Activation and Inhibition of Human Immunodeficiency Virus Entry by a Specific PF-68742 Stereoisomer.

Human immunodeficiency virus (HIV-1) entry into cells is mediated by the viral envelope glycoprotein (Env) trimer, which consists of three gp120 exterior glycoproteins and three gp41 transmembrane glycoproteins. When gp120 binds sequentially to the receptors CD4 and CCR5 on the target cell, the metastable Env trimer is triggered to undergo entry-related conformational changes. PF-68742 is a small molecule that inhibits the infection of a subset of HIV-1 strains by interfering with an Env function other than receptor binding.

Acetylcholine promotes binding of α-conotoxin MII at α3 β2 nicotinic acetylcholine receptors.

α-Conotoxin MII (α-CTxMII) is a 16-residue peptide with the sequence GCCSNPVCHLEHSNLC, containing Cys2-Cys8 and Cys3-Cys16 disulfide bonds. This peptide, isolated from the venom of the marine cone snail Conus magus, is a potent and selective antagonist of neuronal nicotinic acetylcholine receptors (nAChRs). To evaluate the impact of channel-ligand interactions on ligand-binding affinity, homology models of the heteropentameric α3β2-nAChR were constructed.

Homology modeling and molecular docking for the science curriculum.

DockoMatic 2.0 is a powerful open source software program (downloadable from sourceforge.net) that allows users to utilize a readily accessible computational tool to explore biomolecules and their interactions.

Computational evaluations of charge coupling and hydrogen bonding in the active site of a family 7 cellobiohydrolase.

Solution pH and the pKa values of ionizable residues are critical factors known to influence enzyme catalysis, structural stability, and dynamical fluctuations. Presented here is an exhaustive computational study utilizing long time constant pH molecular dynamics, pH replica exchange simulations, and kinetic modeling to evaluate pH-dependent conformations, charge dynamics, residue pKa values, and the catalytic activity-pH profile for cellobiohydrolase Cel7B from Melanocarpus albomyces . The predicted pKa values support the role of Glu212 as the catalytic nucleophile and Glu217 as the acid-base residue.

An ionic liquid dependent mechanism for base catalyzed β-elimination reactions from QM/MM simulations.

Ionic liquids have been proposed to induce a mechanistic change in the reaction pathway for the fundamentally important base-induced β-elimination class compared to conventional solvents. The role of the reaction medium in the elimination of 1,1,1-tribromo-2,2-bis(3,4-dimethoxyphenyl)ethane via two bases, piperidine and pyrrolidine, has been computationally investigated using methanol and the ionic liquids 1-butyl-3-methylimidazolium tetrafluoroborate and hexafluorophosphate [BMIM][BF(4)] and [BMIM][PF(6)], respectively. QM/MM Monte Carlo simulations utilizing free-energy perturbation theory found the ionic liquids did produce a reaction pathway change from an E1cB-like mechanism in methanol to a pure E2 route that is consistent with experimental observations.