Hydrogen (Atom)

This image is a representation of an atom of hydrogen. The cage represents some of the pathways of the electron, seen here shining in purple, as it exists in the 1s orbital. The electron spins around the tiny nucleus containing a proton (not to scale). The color was chosen to match the color of hydrogen plasma

The Influence of Sequence Variability and Dimerization on Mannose Binding in Monocot Mannose Binding Lectins

Abstract Motivation. A model of the lectin from Aloe arborescens was built by homology modeling. Docking studies with mannose were performed on this model and the known crystal structures of monocot mannose binding lectins from snowdrop and garlic. On the basis of these results association of monomers to form dimers is found to be necessary for successful binding of mannose by site III of these lectins, by providing the fourth strand of the -sheet that is a supporting edge for the site. From an analysis of the carbohydrate binding sites (I, II and III) of the above lectins and the docking studies, the mannose binding site I of aloe lectin is predicted to retain the ability to bind mannose with all of the key residues involved in binding unchanged. Site II and III lose residues specific for hydrogen bonding and are predicted to be unable to bind mannose. Aloe lectin monomers are shown to be able to associate as dimers but docking is still unsuccessful in site III. Method. Protein homology modeling and AutoDock docking studies were used in this study. Results. A homology model of aloe lectin was created by both manual and automatic methods and its ability to bind the natural substrate mannose was assessed by docking studies using the genetic algorithm approach in the AutoDock program. The results of the docking studies were correlated with those on lectins for which X-ray crystal data is known and rationalized in terms of specific mutations in the aloe lectin binding sites. Conclusions. Aloe lectin is predicted to be able to bind mannose in its site I binding site, unable to bind in site II because of key residue mutations and also unable to bind in site III

Investigations of two distinct pharmacologically relevant proteins using docking studies and molecular dynamics

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Investigations of two distinct pharmacologically relevant proteins using docking studies and molecular dynamics.

Docking of a flexible ligand to a rigid protein, followed by molecular dynamics (MD) studies to allow movement of the protein is shown to be a useful method for investigating pharmacologically relevant interactions. Studies of MMB lectins (beta-sheet proteins with shallow binding sites) reveal the importance of dimerisation to the activation of all of the carbohydrate binding sites of these lectins, finalising site III into a shape that can accommodate mannose. Aloe lectin was shown to have the overall fold of a MMB lectin and to be capable of forming a dimeric unit, shown to be stable using MD simulations in a water box. Docking shows that only two binding sites in the aloe dimer are thought to be able to bind mannose, as alterations in the residues vital for binding have occurred, and this is supported by the absence of a cluster of docked conformations in these sites. The presence of many 'sticky' patches on the exterior of aloe lectin are observed, revealing extended binding areas consistent with other members of the family. The motions of the mannose molecules in the binding areas during the molecular dynamics simulations suggest that the hydrogen bonds observed in these protein-carbohydrate complexes are dynamic in nature and can be constantly breaking and reforming. Docking of atropine to the GPCR m1AchR (an alpha-helical transmembrane protein with and enclosed binding site) indicates the presence of two key hydrogen bonds with Ser109 and Asn110. The main influences on docking seem to be shape and size of the ligand rather than charge considerations, although the negatively charged end of the binding pocket orients the molecules in the majority of the dockings in the same direction. Docking studies of atropine and selected analogues to m1AchR and two mutants, Tyr381Phe and Tyr381Ala, produce data which correlate well with experimentally determined pIC50 values and a prediction of pIC50 of previously untested antagonists for this system. Molecular dynamics studies show differential movement in the transmembrane helices for MD studies with acetylcholine, atropine and no ligand bound and rearrangement of some key hydrogen bonds. This leads to a model of inverse agonist functionality for atropine and its analogues involving the prevention of helical movement by the aromatic tail groups of these ligands

Bloodlines

Bloodlines is a performance, and a line of practical research into creative, compositional and collaborative strategies in science-engaged performance practices. It conveys the science and psychological experience of life-threatening blood cancer and its treatment through stem cell transplantation