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Ligand Positions (ligand + position)

Distribution by Scientific Domains

Chemistry	75%

Selected Abstracts

Enhanced docking with the mining minima optimizer: Acceleration and side-chain flexibility

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 16 2002
Visvaldas Kairys
Abstract The ligand,protein docking algorithm based on the Mining Minima method has been substantially enhanced. First, the basic algorithm is accelerated by: (1) adaptively determining the extent of each energy well to help avoid previously discovered energy minima; (2) biasing the search away from ligand positions at the surface of the receptor to prevent the ligand from staying at the surface when large sampling regions are used; (3) quickly testing multiple different ligand positions and orientations for each ligand conformation; and (4) tuning the source code to increase computational efficiency. These changes markedly shorten the time needed to discover an accurate result, especially when large sampling regions are used. The algorithm now also allows user-selected receptor sidechains to be treated as mobile during the docking procedure. The energies associated with the mobile side chains are computed as if they belonged to the ligand, except that atoms at the boundary between side chains and the rigid backbone are treated specially. This new capability is tested for several well-known ligand/protein systems, and preliminary application to an enzyme whose substrate is unknown,the recently solved hypothetical protein YecO (HI0319) from Haemophilus influenzae,indicates that side-chains relaxations allow candidate substrates of various sizes to be accommodated. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1656,1670, 2002 [source]

Precise arguments on the distribution of stereospecific active sites on MgCl2 -supported ziegler-natta catalysts

MACROMOLECULAR SYMPOSIA, Issue 1 2004
Boping Liu
Abstract The stereospecific nature of active sites on various MgCl2 -supported Ziegler-Natta catalysts was investigated by stopped-flow technique combined with temperature rising elution fractionation (TREF) method. A modified three-sites model with precise description of the stereospecific nature of various types of active sites stemmed from surface titanium species, Al-alkyl compounds, Mg-compounds and electron donors has been proposed. It was demonstrated that the isospecificity of active sites strongly depends on the bulkiness of the ligands situated at the two most important ligand positions for construction of asymmetry and chirality of the active sites with steric hindrance. In general, there may exist both monometallic and bimetallic sites in heterogeneous Ziegler-Natta catalyst system. The kinds of active titanium species with different chemical structures on this catalyst system should be limited, whereas, the non-discrete distribution of isospecificity of active sites could be considered to generate from the numerous types of steric and electronic effects from the surroundings of active titanium species as well as large number of reversible and dynamic transformation reactions simultaneously occurred on the heterogeneous catalyst surface. [source]

Resolution of ligand positions by site-directed tryptophan fluorescence in tear lipocalin

PROTEIN SCIENCE, Issue 2 2000
Oktay K. Gasymov
Abstract The lipocalin superfamily of proteins functions in the binding and transport of a variety of important hydrophobic molecules. Tear lipocalin is a promiscuous lipid binding member of the family and serves as a paradigm to study the molecular determinants of ligand binding. Conserved regions in the lipocalins, such as the G strand and the F-G loop, may play an important role in ligand binding and delivery. We studied structural changes in the G strand of holo- and apo-tear lipocalin using spectroscopic methods including circular dichroism analysis and site-directed tryptophan fluorescence. Apo-tear lipocalin shows the same general structural characteristics as holo-tear lipocalin including alternating periodicity of a ,-strand, orientation of amino acid residues 105, 103, 101, and 99 facing the cavity, and progressive depth in the cavity from residues 105 to 99. For amino acid residues facing the internal aspect of cavity, the presence of a ligand is associated with blue shifted spectra. The collisional rate constants indicate that these residues are not less exposed to solvent in holo-tear lipocalin than in apo-tear lipocalin. Rather the spectral blue shifts may be accounted for by a ligand induced rigidity in holo-TL. Amino acid residues 94 and 95 are consistent with positions in the F-G loop and show greater exposure to solvent in the holo- than the apo-proteins. These findings are consistent with the general hypothesis that the F-G loop in the holo-proteins of the lipocalin family is available for receptor interactions and delivery of ligands to specific targets. Site-directed tryptophan fluorescence was used in combination with a nitroxide spin labeled fatty acid analog to elucidate dynamic ligand interactions with specific amino acid residues. Collisional quenching constants of the nitroxide spin label provide evidence that at least three amino acids of the G strand residues interact with the ligand. Stern-Volmer plots are inconsistent with a ligand that is held in a static position in the calyx, but rather suggest that the ligand is in motion. The combination of site-directed tryptophan fluorescence with quenching by nitroxide labeled species has broad applicability in probing specific interactions in the solution structure of proteins and provides dynamic information that is not attainable by X-ray crystallography. [source]