Relative stability of homochiral and heterochiral dialanine peptides. Effects of perturbation pathways and force-field parameters on free energy calculations
| Autor: | Wilfred R. Hagen, Jaap A. Jongejan, Yu Zhou, Wilfred F. van Gunsteren, Simon W. de Leeuw, Chris Oostenbrink |
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| Rok vydání: | 2005 |
| Předmět: |
Dipeptide
Chemistry Biophysics Thermodynamic integration Perturbation (astronomy) Dihedral angle Condensed Matter Physics Force field (chemistry) Kinetic resolution chemistry.chemical_compound Crystallography Molecular geometry Computational chemistry Peptide synthesis Physical and Theoretical Chemistry Molecular Biology |
| Zdroj: | Molecular Physics. 103:1961-1969 |
| ISSN: | 1362-3028 0026-8976 |
| Popis: | The relative stability of homochiral (D,D or L,L) and heterochiral (D,L or L,D) dipeptides may have been a decisive factor in the evolutionary propagation of a symmetry-breaking event leading to the present-day predominance of L-amino acids in natural proteins. Kinetic resolution in the solid-phase peptide synthesis of blocked dialanine suggests the activation free energy difference of formation of (D,D or L,L)- and (D,L or L,D)-dialanine to be 0.22 kJ mol−1 in favour of the formation of the homochiral dipeptide. Computer simulation studies were performed on water-solvated dialanine, applying a thermodynamic integration protocol using the GROMOS force field. Five different pathways and three force-field parameter sets have been used to assess the possibility of a computational prediction of the chiral preference. Inversion of the configuration around either one of the Cα-atoms by changing the improper dihedral angle with concomitant relaxation of the bond angles, leads to an excellent reproduction of the ... |
| Databáze: | OpenAIRE |
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