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Conformational Freedom (conformational + freedom)
Selected AbstractsPhased rotation, conformation and translation function: theory and computer programJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 4 2006Frantisek Pavelcik A new crystallographic function, phased rotation conformation and translation (PRCTF), has been developed. The function is designed for automatic interpretation of electron density utilizing molecular fragments with some conformational freedom. A computer program, NUT, has been written for the calculation of the PRCTF. [source] Preparation, characterization, and cellular interactions of collagen-immobilized PDMS surfacesJOURNAL OF APPLIED POLYMER SCIENCE, Issue 1 2008I. Keranov Abstract Multistep procedure to biofunctionalization of (poly)dimethylsiloxane (PDMS) surfaces is present here, including plasma-based Ar+ beam treatment; acrylic acid grafting; and flexible PEG spacer coupling prior to the collagen immobilization by peptide synthesis reaction. The success of any step of the surface modification is controlled by XPS analysis, contact angle measurements, SEM, and AFM observations. To evaluate the effect of PEG chain length, three diNH2PEGs (2000, 6000, and 20,000 D) of relative long polymer chain were employed as a spacer, expecting that a long flexible spacer could provide more conformational freedom for the collagen molecules and fibroblast reorganization to further cellular matrix formation. Human fibroblast cells were used as a model to evaluate the biological response of the collagen-immobilized PDMS surfaces. It is found that the earlier described biofunctionalization is one more road to improvement of the cellular interaction of PDMS, the last one being the best when PEG spacer with moderate chain length, namely of 6000 D, is used. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Direct atomic force microscopy observations of monovalent ion induced binding of DNA to micaJOURNAL OF MICROSCOPY, Issue 3 2004J. S. ELLIS Summary Multivalent ions in solution are known to mediate attraction between two like-charged molecules. Such attraction has proved useful in atomic force microscopy (AFM) where DNA may be immobilized to a mica surface facilitating direct imaging in liquid. Theories of DNA immobilization suggest that either ,salt bridging' or fluctuation in the positions of counter ions about both the mica surface and DNA backbone secure DNA to the mica substrate. Whilst both theoretical and experimental evidence suggest that immobilization is possible in the presence of divalent ions, very few studies identify that such immobilization is possible with monovalent ions. Here we present direct AFM evidence of DNA immobilized to mica in the presence of only monovalent ions. Our data depict E. coli plasmid pBR322 adsorbed onto the negatively charged mica both after short (10 min) and long (24 h) incubation periods. These data suggest the need to re-explore current theories of like-charge attraction to include the possibility of monovalent interactions. We suggest that this DNA immobilization strategy may offer the potential to image natural processes with limited immobilization forces and hence enable maximum conformational freedom of the immobilized biomolecule. [source] Conformation-activity relationships of cyclo -constrained µ/, opioid agonists derived from the N -terminal tetrapeptide segment of dermorphin/deltorphinJOURNAL OF PEPTIDE SCIENCE, Issue 8 2008Sylwia Rodziewicz-Motowid Abstract The N -terminal tetrapeptide segments of dermorphin (Tyr,D -Ala,Phe,Gly,Tyr,Pro,Ser,NH2) and deltorphin (Tyr,D -Ala,Phe,Asp/Glu,Val,Val,Gly,NH2) are agonists at the opioid receptors µ and ,, respectively. [D -Arg2, Lys4]-dermorphin-(1,4) amide (Tyr,D -Arg,Phe,Lys,NH2, DALDA) and [Dmt1]DALDA (where Dmt is 2,,6,-dimethyltyrosine) are among the most potent and selective µ-agonists reported to date, both in vitro (having picomolar µ receptor affinity) and in vivo. In this communication, conformation-activity studies of the following four cyclic analogs of DALDA are presented and discussed: the lead peptide S2,S4 -cyclo (Tyr,D -Cys,Phe,Cys,NH2), constrained by means of an S4.2S4.4 disulfide between Cys2 and Cys4; its two cis and transC4.2C4.4 -olefinic dicarba analogs, and the product of saturation of them both. They are potent nonselective or moderately µ-selective opioid agonists in vitro. They have been synthesized and tested earlier [Berezowska I, Chung NN, Lemieux C, Wilkes BC, and Schiller PW, Acta Biochim Polon 53, 2006, 73,76]. We have studied their conformations using NMR and molecular dynamics. With major conformational constraints imposed by the 11-membered ring spanning residues 2,4, they show well defined conformations of this ring, while the exocylic Tyr1 and Phe3 side chains still have significant conformational freedom. The more active and selective µ versus , disulfide and saturated dicarba agonists seem to have in common: (i) their ring structures more flexilble than those of the other two and (ii) their ring structures similar to each other and more diverse than those in the other two. Given this and the small size of the peptides having confirmed bioactivity profiles, there is a chance that their conformations determined in solution approach receptor-bound conformations. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. [source] A theoretical study of pentacyclo-undecane cage peptides of the type [Ac-X-Y-NHMe]JOURNAL OF PEPTIDE SCIENCE, Issue 2 2006Krishna Bisetty Abstract The conformational preferences of peptides of the type, Ac-X-Y-NHMe, where X and Y = Ala, cage and Pro, were studied by means of computational techniques within the framework of a molecular mechanics approach. For each of the eight peptide analogues, extensive conformational searches were carried out using molecular dynamics (MD) and simulated annealing (SA) protocols in an iterative fashion. Both results are in good agreement and complement each other. The conformational search indicates that the cage residue restricts the conformational freedom of the dipeptide considerably in comparison with the other model residues used. This study revealed that proline exhibits a greater tendency in promoting reverse-turn characteristics in comparison to the cage peptides, which show promising ,-turn characteristics. It was also found that 300,500 K is not sufficient to overcome rotational barriers for cage peptides. In all cases, the low-energy conformers have a tendency to form bent structures. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] DNA and RNA-Controlled Switching of Protein Kinase ActivityCHEMBIOCHEM, Issue 4 2009Lars Röglin Dr. Abstract Constrained: The readily programmable nucleic acid mediated recognition is used to constrain a phosphopeptide that was flanked by PNA segments. RNA-based switching allows control over the activity of target enzymes such as the protein kinase Src. It might thus be feasible to transduce changes of the concentration of selected RNA molecules to changes of the activity of signal transduction proteins. Protein switches use the binding energy gained upon recognition of ligands to modulate the conformation and binding properties of protein segments. We explored whether the programmable nucleic acid mediated recognition might be used to design or mimic constraints that limit the conformational freedom of peptide segments. The aim was to design nucleic acid,peptide conjugates in which the peptide portion of the conjugate would change the affinity for a protein target upon hybridization. This approach was used to control the affinity of a PNA,phosphopeptide conjugate for the signal transduction protein Src kinase, which binds the cognate phosphopeptides in a linear conformation. Peptide,nucleic acid arms were attached to known peptide binders. The chimeric molecules were studied in three modes: 1) as single strands, 2) constrained by intermolecular hybridization (duplex formation) and 3) constrained by intramolecular hybridization (hairpin formation). Of note, duplexes that were designed to accommodate bulged peptide structures (for example, in hairpins or bulges) had lower binding affinities than duplexes in which the peptide was allowed to adopt a more relaxed conformation. Greater than 90-fold differences in binding affinities were observed. It was, thus, feasible to make use of DNA hybridization to reversibly switch from no to almost complete inhibition of Src-SH2,peptide binding, and vice versa. A series of DNA and PNA-based hybridization experiments revealed the importance of charges and conformational effects. Nucleic acid mediated switching was extended to the use of RNA; this enabled a regulation of the enzymatic activity of the Src kinase. The proof-of-principle results demonstrate for the first time that PNA,peptide chimeras can transduce changes of the concentration of a given RNA molecule to changes of the activity of a signal transduction enzyme. [source] Cyclic ,-Tetra- and Pentapeptides: Synthesis through On-Resin Cyclization and Conformational Studies by X-Ray, NMR and CD Spectroscopy and Theoretical CalculationsCHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2005Frank Büttner Dr. Abstract The solution-phase synthesis of the simplest cyclic ,-tetrapeptide, cyclo(,-Ala)4 (4), as well as the solid-phase syntheses through side chain anchoring and on-resin cyclization of the cyclic ,3 -tetrapeptide cyclo(-,3hPhe-,3hLeu-,3hLys-,3hGln-) (14) and the first cyclic ,3 -pentapeptide cyclo(-,3hVal-,3hPhe-,3hLeu-,3hLys-,3hLys-) (19) are reported. Extensive computational as well as spectroscopic studies, including X-ray and NMR spectroscopy, were undertaken to determine the preferred conformations of these unnatural oligomers in solution and in the solid state. cyclo(,-Ala)4 (4) with no chiral side chains is shown to exist as a mixture of rapidly interchanging conformers in solution, whereas inclusion of chiral side chains in the cyclo-,3 -tetrapeptide causes stabilization of one dominating conformer. The cyclic ,3 -pentapeptide on the other hand shows larger conformational freedom. The X-ray structure of achiral cyclo(,-Ala)4 (4) displays a Ci -symmetrical 16-membered ring with adjacent CO and N-H atoms pointing pair wise up and down with respect to the ring plane. CD spectroscopic examinations of all cyclic ,-peptides were undertaken and revealed results valuable as starting point for further structural investigations of these entities. [source] Synthesis, chiroptical properties, and their theoretical simulation of some highly rotating benzotricamphor derivatives,,CHIRALITY, Issue 1E 2009Giuseppe Mazzeo Abstract The large molecules 1,3 (69, 90, and 102 atoms, respectively), prepared by cyclotrimerization of enantiomerically pure derivatives of (,)-bornyl acetate, show intense ECD spectra, high optical rotation (OR) values (200,1300, in absolute value) dominated in sign and order of magnitude by the lowest-energy Cotton effects, that is, they are the ideal candidates to test the reliability of our "approximate" (TDDFT/B3LYP/6-31G* or smaller basis set) approach to the calculation of chiroptical properties. As a matter of fact, a correct simulation of the OR values and ECD spectra of 1 and 2 can be obtained even using STO-3G basis set and semiempirical or molecular mechanics input geometries: for 1, at the TDDFT/B3LYP/STO-3G level, the OR values are of the order of 500,550, versus an experimental value ranging between 660 and 690, depending on the solvent. On the contrary, the case of 3 (exp. OR between ,1330 and ,1500) is really complex (for instance, the OR values range between ,3216 and ,729 (TDDFT/B3LYP/6-31G* calculations) or ,1824 and ,444 (TDDFT/B3LYP/STO-3G calculations)), making the comparison between calculated and experimental values more difficult. The behavior of 3 is due to its molecular flexibility, whereas 1 is a really rigid molecules and 2 behaves (vide infra) as it were a rigid system. These observations strongly indicate that the conformational freedom constitutes one of the major difficulties for a correct but simple simulation of the chiroptical properties. Chirality 21:E86,E97, 2009. © 2009 Wiley-Liss, Inc. [source] | ||||||||||