Figure - available from: Journal of Protein Chemistry
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Backbone ribbon (orange) and side chain stick representation of the computed structures for the p53 negative regulatory domain peptide 374–388: leftmost structure, lowest energy all-α-helix structure. Central structure, most probable structure: thick ribbon represents the α-helical segment (residues Gly 374–Lys 381); thin ribbon represents succeeding helical structure (Lys 382–Glu 388). Rightmost structure: global minimum structure showing β-structure (thin orange ribbon rod) followed by anti-parallel α-helix. Numbering system: the residue numbers shown in this figure are the sequence numbers for the isolated peptide including the CH3–C=O and NHCH3 end groups. The correspondence of these numbers with the numbering of these residues in the p53 protein is as follows:
Source publication
We have computed the low energy conformations of the negative regulatory domain of p53, residues 374–388 using Empirical Conformational Energies of Peptides Program including solvation and computed the statistical weights of distinct conformational states. We find that there are two high probability conformations, one an α-helix from Lys 374–Lys 38...
Citations
... As described previously [12], the conformations that were computed to have total conformational energies, i.e., ECEPP energy + hydration energy, that were ≤ 5 kcal/mole, as listed for each step in the chain build-up procedure were retained. All possible combinations of conformations of these resulting minima were generated with the single residue minima of the next amino acid in the sequence, and the above process was repeated. ...
... For each of the minima for each of the two tetrapeptides, conformation letter states as defined in Ref. [10] were assigned to each set of backbone dihedral angles for each residue. The conformational state is then defined as the conformational letter sequence for each minimum as described previously [12,13]. We then computed the Boltzmann probabilities of occurrence for all of the resulting minima. ...
... In addition, we computed single residue probabilities for each residue in a given conformational state as described previously [12,13]. ...
We have computed the low energy minima for the two endomorphin peptides, N-acetyl-Tyr-Pro-Trp-Phe-NHCH3 (endomorphin 1) and Tyr-Pro-Phe-Phe-NHCH3 (endomorphin 2) in aqueous solution. These peptides block pain without inducing the harmful side effects of the opiates that bind to the same mu opiate receptor but have short half lives. From over 1000 starting conformations for each peptide, we find less than 200 low energy structures whose conformational energies were ≤ 5 kcal/mole of the energy of the global minimum. The most probable conformations calculated using the Boltzmann distribution for both peptides were similar to one another. Using the letter representation for backbone conformational states, these most probable structures were D A E E for endomorphin 1 and E A E E for endomorphin 2. Both of these structures form reverse turns at Pro 2-Trp (Phe) 3 resulting in the juxtaposition of the aromatic rings of Tyr 1 and Phe 4. The Trp residue of endomorphin 1 points to the back of the reverse turn. These features may be useful in the design of non-peptide analogues that will have longer half-lives than the peptides.
