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Atomic Details (atomic + detail)
Selected AbstractsSynthetic polymers containing ,-amino acids: from polyamides to poly(ester amide)s,JOURNAL OF PEPTIDE SCIENCE, Issue 5 2005Jordi Puiggalí Abstract Polyamides and poly(ester amide)s which contain glycine residues as a comonomer show unique features. In collaboration with Professor M. Goodman we carried out studies on low molecular weight models which allow a structural analysis with atomic detail. In this way, sequential polyamides constituted by glycine and ,-amino acids may adopt new structures characterized by a network of intermolecular hydrogen bonds that are established along three directions at 120°. This peculiar structure is based on the conformational preferences of glycine residues. X-ray and electron microscopy studies on poly(ester amide)s indicate a structure constituted by a stacking of hydrogen bonded sheets. Differences have been found in the shift between consecutive sheets. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Dynamical view of membrane binding and complex formation of human factor VIIa and tissue factorJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2010Y. Z. OHKUBO Summary.,Background:,The molecular mechanism of enhancement of the enzymatic activity of factor VIIa by tissue factor (TF) is not fully understood, primarily because of the lack of atomic models for the membrane-bound form of the TF,FVIIa complex. Objectives:,To construct the first membrane-bound model of the TF,FVIIa complex, and to investigate the dynamics of the complex in solution and on the surface of anionic membranes by using large-scale molecular dynamics (MD) simulations in full atomic detail. Methods:,Membrane-bound models of the TF,FVIIa complex and the individual factors were constructed and subjected to MD simulations, in order to characterize protein,protein and protein,lipid interactions, and to investigate the dynamics of TF and FVIIa. Results:,The MD trajectories reveal that isolated FVIIa undergoes large structural fluctuation, primarily due to the hinge motions between its domains, whereas soluble TF (sTF) is structurally stable. Upon complex formation, sTF restricts the motion of FVIIa significantly. The results also show that, in the membrane-bound form, sTF directly interacts with the lipid headgroups, even in the absence of FVIIa. Conclusion:,The first atomic models of membrane-bound sTF,FVIIa, FVIIa and sTF are presented, revealing that sTF forms direct contacts with the lipids, both in the isolated form and in complex with FVIIa. The main effect of sTF binding to FVIIa is spatial stabilization of the catalytic site of FVIIa, which ensures optimal interaction with the substrate, FX. [source] Molecular Dynamics Simulations of the Orientation and Reorientational Dynamics of Water and Polypyrrole Rings as a Function of the Oxidation State of the PolymerMACROMOLECULAR THEORY AND SIMULATIONS, Issue 1 2005Jose J. López Cascales Abstract Summary: Polypyrrole is one of the most widely-studied conducting polymers due to its steady electrochemical response and good chemical stability in different solvents, including organic and inorganic ones. In this work, we provide for the first time valuable information in atomic detail concerning the steady and dynamic properties of pyrrole rings as a function of the oxidation state of the polymer. The study was carried out by Classical molecular dynamics simulation, where the system was modelled by 256 polypyrrole chains of 10 pyrrole rings each. Water was explicitly introduced in our simulations. Besides the uncharged or reduced state, two steady oxidation states of the polymer have been simulated by introducing a net charge (+1) on 85 and 256 of the polypyrrole chains. To balance the charges emerging in these oxidised states, 85 and 256 chloride ions (Cl,1) respectively, were introduced into the system. From an analysis of the simulated trajectories, the orientation and relaxation times of water and pyrrole rings were evaluated for the different oxidation states of the polymer across the polypyrrole/water interface. The calculated densities for different oxidation states describe the swelling or shrinking process during electrochemical oxidation or reduction respectively. The rotational relaxation times calculated for the polypyrrole rings decrease with increasing oxidation of the polymer, which is in a good agreement with experimental electrochemical data. Almost no variation in pyrrole ring orientation was measured for the different oxidation states of the polymer, even compared with polypyrrole bulk. As regards the water structure in the vicinity of the polypyrrole/water interface, both the orientation and orientation relaxation time were strongly affected by the presence of charges in the polymer. Thus, the water dipole was strongly orientated in the vicinity of the water/polypyrrole interface and its orientational relaxation time increased by one order of magnitude compared with bulk water, even when only one-third of the total polymer chains were oxidised. The results attained in this work were validated with experimental results, when they were available. Polypyrrole ring orientation and water orientation at the polypyrrole/water interface. (a) 256 rPPy and (b)171 rPPy,+,85 oPPy. [source] pKa optimized catalysis in serine proteinases, an ab initio study on the catalaytic HisINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 11 2007Péter Hudáky Abstract First principle models of catalytic apparatus of enzymes can be used for studying stability as well as the atomic details of a catalytic mechanism. For example, the catalytic triad of chymotrypsin was recently investigated by using an ab initio geometry optimized (Hudáky and Perczel, Proteins: Struct Funct Genet, 2006, 62, 749) self-stabilizing molecule ensemble without the presence of the complete enzyme and substrate. Several parameters of the above catalytic reaction turned out to be the same within the model and the in vitro enzymatic reaction. Among the numerous parameters of the catalytic process geometrical changes of the catalytic histidine was investigated here and the variation of its pKa value was determined. A relatively large range, 3.5 unit, was determined as the variation of pKa as function of the conformational subspace available in serine proteases. Comparing PDB structures of the free and the complex enzymes it was shown, that histidine, after accepting the proton from the OH group of the catalytic serine, undergoes a minor conformational change accompanied by a 2.5 unit decrease in pKa. We conclude that the changes of pKa during catalysis are predominantly determined by the geometrical arrangement of the histidine moiety and this change serves as a significant driving force in the catalytic process. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source] Mechanistic insights into oxidosqualene cyclizations through homology modelingJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2003Gasch, Tanja Schulz Abstract 2,3-Oxidosqualene cyclases (OSC) are key enzymes in sterol biosynthesis. They catalyze the stereoselective cyclization and skeletal rearrangement of (3S)-2,3-oxidosqualene to lanosterol in mammals and fungi and to cycloartenol in algae and higher plants. Sequence information and proposed mechanism of 2,3-oxidosqualene cyclases are closely related to those of squalene-hopene cyclases (SHC), which represent functional analogs of OSCs in bacteria. SHCs catalyze the cationic cyclization cascade converting the linear triterpene squalene to fused ring compounds called hopanoids. High stereoselectivity and precision of the skeletal rearrangements has aroused the interest of researchers for nearly half a century, and valuable data on studying mechanistic details in the complex enzyme-catalyzed cyclization cascade has been collected. Today, interest in cyclases is still unbroken, because OSCs became targets for the development of antifungal and hypocholesterolemic drugs. However, due to the large size and membrane-bound nature of OSCs, three-dimensional structural information is still not available, thus preventing a complete understanding of the atomic details of the catalytic mechanism. In this work, we discuss results gained from homology modeling of human OSC based on structural information of SHC from Alicyclobacillus acidocaldarius and propose a structural model of human OSC. The model is in accordance with previously performed experimental studies with mechanism-based suicide inhibitors and mutagenesis experiments with altered activity and product specificity. Structural insight should strongly stimulate structure-based design of antifungal or cholesterol-lowering drugs. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 741,753, 2003 [source] Stereoselectivity of Pseudomonas cepacia lipase toward secondary alcohols: A quantitative modelPROTEIN SCIENCE, Issue 6 2000Tanja Schulz Abstract The lipase from Pseudomonas cepacia represents a widely applied catalyst for highly enantioselective resolution of chiral secondary alcohols. While its stereopreference is determined predominantly by the substrate structure, stereoselectivity depends on atomic details of interactions between substrate and lipase. Thirty secondary alcohols with published E values using P. cepacia lipase in hydrolysis or esterification reactions were selected, and models of their octanoic acid esters were docked to the open conformation of P. cepacia lipase. The two enantiomers of 27 substrates bound preferentially in either of two binding modes: the fast-reacting enantiomer in a productive mode and the slow-reacting enantiomer in a nonproductive mode. Nonproductive mode of fast-reacting enantiomers was prohibited by repulsive interactions. For the slow-reacting enantiomers in the productive binding mode, the substrate pushes the active site histidine away from its proper orientation, and the distance d(HN, , Oalc) between the histidine side chain and the alcohol oxygen increases. d(HN, , Oalc) was correlated to experimentally observed enantioselectivity: in substrates for which P. cepacia lipase has high enantioselectivity (E > 100), d(HN, , Oalc) is>2.2 Ĺ for slow-reacting enantiomers, thus preventing efficient catalysis of this enantiomer. In substrates of low enantioselectivity (E < 20), the distance d(HN, , Oalc) is less than 2.0 Ĺ, and slow- and fast-reacting enantiomers are catalyzed at similar rates. For substrates of medium enantioselectivity (20 < E< 100), d(HN, , Oalc) is around 2.1 Ĺ. This simple model can be applied to predict enantioselectivity of P. cepacia lipase toward a broad range of secondary alcohols. [source] Structure of Escherichia coli uridine phosphorylase at 2.0,ĹACTA CRYSTALLOGRAPHICA SECTION D, Issue 1 2003F. Temple Burling The 2.0,Ĺ crystal structure has been determined for Escherichia coli uridine phosphorylase (UP), an essential enzyme in nucleotide biosynthesis that catalyzes the phosphorolytic cleavage of the C,N glycosidic bond of uridine to ribose-1-phosphate and uracil. The structure determination of two independent monomers in the asymmetric unit revealed the residue composition and atomic details of the apo configurations of each active site. The native hexameric UP enzyme was revealed by applying threefold crystallographic symmetry to the contents of the asymmetric unit. The 2.0,Ĺ model reveals a closer structural relationship to other nucleotide phosphorylase enzymes than was previously appreciated. [source] | ||||||||||