Enkephalin: Structure‐function relationships

Balodis, Yu.Yu.; Nikiforovich, Gregory V.; Grinsteine, I.V.; Vegner, R.E.; Chipens, G. I.

doi:10.1016/0014-5793(78)80570-5

Cited by 40 publications

(15 citation statements)

References 16 publications

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“…A conclusion can be drawn in comparison of our results with other previous attempts, using the ECEPP force field and many different search strategies, to find a global minimum and to obtain a set of low-energy conformers [1,[4][5][6][7]. Differences in the results obtained must be due to the limitations imposed by the geometry constraints of the ECEPP force field rather than differences in search strategies.…”

Section: Description Of the Unique Low-energy Conformational Domains mentioning

confidence: 58%

“…Many additional low-energy bend structures were also reported. Theoretical calculations carried out by other investigators also reported a bend structure [3,4] as the most stable conformation. In more recent work, Scheraga [5][6][7][8] continued to study the performance of different searching methods in identifying the global minimum structure using, as a reference for the success of the search, the first candidate G-P 13-II' turn found.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of low-energy conformational domains for Met-enkephalin

Pérez¹,

Villar²,

Loew³

1992

J Computer-Aided Mol Des

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An extensive exploration of the conformational hypersurface of Met-enkephalin has been carried out, in order to characterize different low-energy conformational domains accessible to this pentapeptide. The search strategy used consisted of two steps. First, systematic nested rotations were performed using the ECEPP potential. Ninety-two low-energy structures were found and minimized using the CHARMm potential. High and low-temperature molecular dynamics trajectories were then computed for the lowest energy structures in an interative fashion until no lower energy conformers could be found. The same search strategy was used in these studies simulating three different environments, a distance-dependent dielectric epsilon = r, and two constant dielectrics epsilon = 10 and epsilon = 80. The lowest energy structure found in a distance-dependent dielectric is a Gly-Gly beta-II'-type turn. All other structures found for epsilon = r within 10 kcal/mol of this lowest energy structure are also bends. In the more polar environments, the density of conformational states is significantly larger compared to the apolar media. Moreover, fewer hydrogen bonds are formed in the more polar environments, which increases the flexibility of the peptide and results in less structured conformers. Comparisons are made with previous calculations and experimental results.

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Section: Description Of the Unique Low-energy Conformational Domains mentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Characterization of low-energy conformational domains for Met-enkephalin

Pérez¹,

Villar²,

Loew³

1992

J Computer-Aided Mol Des

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“…It is important to mention the contribution of the Tyrl OH" in the stabilisation of folded structures. Most theoretical (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) and experimental (21)(22)(23)(24)(25)(26) studies have proposed such conformations. Figure 3a gives the superposition of the structures belonging to this group.…”

Section: Conformational Domains Of Met-enkephalinmentioning

confidence: 99%

“…Both theoretical results (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) and NMR largest part of the conformational space is sampled by gen-, erating a large number of initial random conformations.…”

Section: Introductionmentioning

confidence: 99%

Low-energy conformational domains of polypeptides, characterized by a random-search and minimization procedure

Michel¹,

Ameziane-Hassani²,

Bredin³

1992

Can. J. Chem.

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This paper is declicntecl t o Professor Sigeru Huzinaga on the occnsion ($his 65th birthdclyANDRE G. MICHEL, CHAKIB AMELIANE-HASSANI, and NATHALIE BREDIN. Can. J. Chenl. 70, 596 (1992). In the framework of molecular mechanics conformational energy calculations, a random-search and minimization procedure is presented to characterize low-energy domains of polypeptidic structures. Rather than striving for global minima, populations of conformers are randomly generated, and their energy is minimized in order to study their intrinsic properties. The application to the opioid peptide Met-Enkephalin allowed the identification of low-energy domains that are compared with previous results of conformational studies on this molecule. Our method gives a complete overview of the conformational behaviour of the polypeptide under study, including previously reported structures as determined from experimental and theoretical studies. To illustrate the usefulness of this method to determine bioactive peptidic structures and their active conformers, the application to geometrically constrained chemotactic tripeptides is presented.Key words: peptides, conformation, theoretical prediction.ANDRT. G. MICHEL, CHAKIB AMEZIANE-HASSANI et NATHALIE BREDIN. Can. J. Chem. 70, 596 (1992). Une mCthode thCorique de caractCrisation des domaines conformationnels des molCcules polypeptidiques est presentee. Les calculs d'Cnergie conformationnelle sont effectuCs dans le cadre empirique de la mCcanique molCculaire. PlutBt que chercher B localiser le minimum global d'une hypersurface CnergCtique, des populations de conform6res sont gCnCrees en vue d'en Ctudier les propriCtCs intrinskques. L'application au peptide opiact Met-Enktphaline a permis d'identifier des domaines dans la population gCnerCe et de comparer ces rCsultats des Ctudes conformationnelles antkrieures. On dCmontre que cette approche fournit une vue complkte du comportement conformationnel du polypeptide, incluant les structures proposkes par des travaux thCoriques ou expCrimentaux. Afin d'illustrer I'applicabilitC de la mCthode pour I'identification de conformation d'intCr&t biologique, une Ctude a kt6 menCe sur des tripeptides chimiotactiques a gCometrie restreinte.

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“…2). Balodis et a1 [27] use a different approach to generate starting minimum energy conformers but also compare [D-Ala2] and [D-Ala3] analogs with MENK and obtain a backbone configuration similar to that of De Coen ( Table I) Several groups have incorporated analog information into their energy studies in an attempt to deduce the receptor-bound conformation of enkephalin. The approach has the advantage that some of the tacit assumptions made by the calculations, such as parametrization and neglect of solvent, are internally consistent with such comparisons.…”

Section: Jss:33mentioning

confidence: 99%

Elucidation of the receptor‐bound conformation of the enkephalins

et al. 1978

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The biologically relevant conformers of enkephalin predicted by solid state, solution state, and theoretical energy studies have been compared with the published structure-activity data on these compounds. No conformational technique proposes a model consistent with all the pharmacological data; the shortcomings of each approach are evaluated. An alternative approach, which correlates the structure-activity data of opiate compounds with that of the enkephalins, is described and shown to produce a model consistent with the available structure-activity data.

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Enkephalin: Structure‐function relationships

Cited by 40 publications

References 16 publications

Characterization of low-energy conformational domains for Met-enkephalin

Characterization of low-energy conformational domains for Met-enkephalin

Low-energy conformational domains of polypeptides, characterized by a random-search and minimization procedure

Elucidation of the receptor‐bound conformation of the enkephalins

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