Cqx

Fig. 6.3 Backbone atom-positional root-mean-square deviation (residues 2-6) of MD trajectory structures with respect to the 314-helical model structure derived from NMR data for a b-heptapeptide (see Panel A, Fig. 6.1) in methanol for simulations with different charge states of the terminal residues. Upper panel: the N terminus is charged and the C terminus is uncharged (NH3+, COOH); middle panel: the N terminus is uncharged and the C terminus is charged (NH2, COO-); lower panel: both termini are uncharged (NH2, COOH) [24].

Fig. 6.5 Backbone atom-positional root-mean-square deviation (residues 2-6) of MD trajectory structures with respect to the 314-helical conformation as a function of time for four b-depsiheptapeptides (see Fig. 6.6) at 298 K and 340 K. For peptide pepOnone the NMR model structure was used as the 314-

helical reference structure, whereas for all other peptides a canonical 314-helical conformation was taken as reference. The pepOnone notation stands for the 7-b-peptide the structure of which is shown in panel A of Fig. 6.1.

Fig. 6.5 Backbone atom-positional root-mean-square deviation (residues 2-6) of MD trajectory structures with respect to the 314-helical conformation as a function of time for four b-depsiheptapeptides (see Fig. 6.6) at 298 K and 340 K. For peptide pepOnone the NMR model structure was used as the 314-

helical reference structure, whereas for all other peptides a canonical 314-helical conformation was taken as reference. The pepOnone notation stands for the 7-b-peptide the structure of which is shown in panel A of Fig. 6.1.

fold, neither in water nor in methanol, in agreement with NMR data [32]. A very short 3-b-aminoxypeptide was shown to adopt a very stable 1.8s-helix in chloroform and to exhibit no particular fold in water, again in agreement with NMR data [33]. Figure 6.5 shows the effect of replacing an N-H group by an O atom in residue 2 (pep O2), or residue 4 (pep O4), or residue 6 (pep O6), or all residues (pep Oan) in 7-b-peptides (Fig. 6.6) that are very similar to the 7-b-peptide (pepOnone) discussed before. The population of the 314-helical fold decreases from pepOnone to pepO6 to pepO2 to pepO4 to pepOan, in agreement with NMR data

[34]. Whether the N or C termini of a b-peptide are carrying protective groups or not, also influences the stability of the helical fold in agreement with experiment

Which particular fold (see Chapter 2) a b-peptide will adopt depends on the type of side chain and whether the side chain is located at the a-position (b2-peptide) or at the b-position (b3-peptide) in the backbone. The folds observed in NMR experiments were all reproduced in MD simulations based on the GROMOS force field: a left-handed (M)-314 helix [12], a right-handed (P)-10/12 helix [13], a right-handed (P)-2.512 helix [36], or a b-hairpin [18]. Substitution of two methyls at the b-positions in conjunction with standard side chains at the pepOnone pep02

pep 04

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