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Conformational Profile (conformational + profile)
Selected AbstractsComparative analysis of the conformational profile of substance P using simulated annealing and molecular dynamicsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 16 2004Francesc J. Corcho Abstract The present study describes an extensive conformational search of substance P using two different computational methods. On the one hand, the peptide was studied using the iterative simulated annealing, and on the other, molecular dynamics simulations at 300 and 400 K. With the former method, the peptide was studied in vacuo with a dielectric constant of 80, whereas using the latter study the peptide was studied in a box of TIP3P water molecules. Analysis of the results obtained using both methodologies was carried out using an in-house methodology using a cluster analysis method based on information theory. Comparison of the two sampling methodologies and the different environment used in the calculations is also analyzed. Finally, the conformational motifs that are characteristic of substance P in a hydrophilic environment are presented and compared with the experimental results available in the literature. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1937,1952, 2004 [source] Study of the conformational profile of the norbornane analogues of phenylalanineJOURNAL OF PEPTIDE SCIENCE, Issue 6 2002Arnau Cordomí Abstract The conformational profile of the eight stereoisomeric 2-amino-3-phenylnorbornane-2-carboxylic acids (2-amino-3-phenylbicyclo[2.2.1]heptane-2-carboxylic acids) has been assessed by computational methods. These molecules constitute a series of four enantiomeric pairs that can be considered as rigid analogues of either L - or D -phenylalanine. The conformational space of their N -acetyl methylamide derivatives has been explored within the molecular mechanics framework, using the parm94 set of parameters of the AMBER force field. Local minimum energy conformations have been further investigated at the ab initio level by means of the Hartree-Fock and second order Moller-Plesset perturbation energy calculations using a 6,31G(d) basis set. The results of the present work suggest that the bulky norbornane structure induces two kinds of conformational constraints on the residues. On one hand, those of a steric nature directly imposed by the bicycle on the peptide backbone and, on the other hand, those that limit the orientations attainable by the phenyl ring which, in turn, reduces further the flexibility of the peptide backbone. A comparative analysis of the conformational profile of the phenylnorbornane amino acids with that of the norbornane amino acids devoid of the ,-phenyl substituent suggests that the norbornane system hampers the residue to adopt extended conformations in favour of C7-like structures. However, the bicycle itself does not impart a clear preference for any of the two possible C7 minima. It is the aromatic side chain, which is forced to adopt an almost eclipsed orientation, that breaks this symmetry introducing a marked preference for a single region of the (,, ,) conformational space in each of the phenylalanine norbornane analogues investigated. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] Analysis of the conformational profile of trishomocubane amino acid dipeptideBIOPOLYMERS, Issue 5 2006Krishna Bisetty Abstract 4-Amino-(D3)-trishomocubane-4-carboxylic acid is a constrained ,-amino acid residue that exhibits promising conformational characteristics, i.e., helical and ,-turns. As part of the development of conformational guidelines for the design of peptides and protein surrogates, the conformational energy calculations on trishomocubane using molecular mechanics and ab initio methods are presented. The C, carbon of trishomocubane forms part of the cyclic structure, and consequently a peptidic environment was simulated with an acetyl group on its N-terminus and a methylamide group on its C-terminus. Ramachandran maps computed at the molecular mechanics level using the standard AMBER (parm94) force field libraries compared reasonably well with the corresponding maps computed at the Hartree Fock level, using the 6-31G* basis set. Trishomocubane peptide (Ac-Tris-NHMe) is characterized by four low energy conformers corresponding to the C7ax, C7eq, 310, and ,L helical structures. © 2005 Wiley Periodicals, Inc. Biopolymers 81: 339,349, 2006 This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Design of Cyclopentaisoxazoline Amino Acids as Conformationally Constrained Agonists at Glutamate ReceptorsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2003Paola Conti Abstract We have prepared four isomeric 3-hydroxycyclopentaisoxazoline amino acids 12,15, which represent analogues of glutamic acid having restricted conformations, through a strategy based on the 1,3-dipolar cycloaddition of bromonitrile oxide to a suitably protected 1-aminocyclopent-2-enecarboxylic acid. These target compounds proved to be inactive when assayed at ionotropic and metabotropic glutamate receptors, except for 12 which is an agonist primarily at mGluR5 (EC50 = 79 ,M), but is less active at mGluR2 and only marginally active at mGluR1. The biological data are accounted for through comparison of the conformational profiles of the test compounds with that of reference agonists, i.e., N -methyl- D -aspartate (NMDA, 2), and 1-aminocyclopentane-1,3-dicarboxylic acids [trans -ACPD, 10; cis -ACPD, 11]. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Evaluation of the conformational propensities of peptide isosteres as a basis for selecting bioactive pseudopeptidesCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2001S. Gupta Abstract: Our aim was to compare the repertoires of conformers formed by the model zwitterionic peptides AA and AAA in aqueous solution with the conformational profiles of a range of their peptide isosteres, so as to facilitate selection of isosteres for synthesis and testing as biologically stable surrogates of bioactive di- and tripeptides. Comparisons were based upon the results of conformational analysis using a random search approach implemented within the SYBYL molecular modelling package, using zwitterionic molecules, simulated aqueous solvation using a dielectric constant of 80 and allowing all torsions to vary. For each compound, individual conformers were grouped on the basis of specific combinations of psi, phi and omega torsions and, using their energies, the aggregated percentage for each group was calculated using a Boltzmann distribution and displayed using a 3D pseudo Ramachandran plot relating percentage conformer to psi and phi torsions. Retroamide, N -methylamide and thioamide isosteres showed the best match to natural peptides and to the molecular recognition parameters defined for substrates of peptide transporters. The results should aid rational design of therapeutic agents in various areas, e.g. oral delivery of drugs by peptide transporters and of peptidase inhibitors. This approach may usefully be applied to various biochemical and pharmaceutical topics. [source] | ||||||||||