Characterization of the conformational domains of bradykinin by computational methods

Abstract

The AMBER 4.0 force field was used to perform a characterization of the conformational profile of the nonapeptide bradykinin. A thorough conformational search was carried out using molecular dynamics as sampling technique, by computing cycles of high (900 K) and low (300 K) temperature trajectories. A total of 2400 minima were generated and subsequently clustered using the root-mean-square of the backbone dihedral angles as criterium. After the use of a tolerance value of 20 degrees, the conformations were clustered in 233 unique conformations with energies up to 40 kcal/mol above the lowest minimum. The analysis of the low-energy conformations indicate that the peptide exhibits a high tendency to adopt a beta-turn at the C-terminus and a propensity to adopt a bent structure at the N-terminus. These results are in agreement with the experimental evidence reported in the literature and provide detailed information necessary to understand the conformational preferences of the peptide.

Threonine6-Bradykinin: Structural Characterization in the Presence of Micelles by Nuclear Magnetic Resonance and Distance Geometry

“…Most of the structures are found to populate a β-turn of type I or II in the residues 6-9. This particular structure has been predicted as favorable for BK from molecular dynamics studies by Perez 60 and with simulated annealing calculations by Salvino. 61 There is evidence of a tendency of BK to fold into a bent structure at the C-terminus also in solvent systems such as dioxane:water, 9:1, and dimethyl sulfoxide and in the presence of lisophosphatidylcholine micelles.…”

“…Most of the structures are found to populate a β-turn of type I or II in the residues 6−9. This particular structure has been predicted as favorable for BK from molecular dynamics studies by Perez and with simulated annealing calculations by Salvino …”

Theoretical evidence of a salt bridge disruption as the initiating process for the α1d‐adrenergic receptor activation: A molecular dynamics and docking study

“…The analysis of the different spatial arrangements of the three ECLs was conducted by using as a sampling technique the combination of cycles of high (600 K) and low (300 K) temperature trajectories of molecular dynamics. The procedure is an adaptation of an approach that has been already used to characterize the low‐energy domains for small and medium‐size peptides 26, 27. Specifically, an initial library of conformations is created by means of the snapshots of a first molecular dynamics run at high temperature.…”

Probing the Topological Arrangement of the N- and C-Terminal Residues of Bradykinin for Agonist Activity at the B1 Receptor

“…The general consensus from conformational studies is that BK exists in many conformational states in aqueous solution, while in alternative solvent systems (dimethyl sulfoxide, sodium dodecyl sulfate micelles, dioxane:water) there is a tendency for the C-terminus to adopt a turn-like structure. − A C-terminal β-turn was predicted to be energetically favorable from theoretical studies , and has been successfully utilized in the design of agonists and antagonists. ,− The highly potent BK antagonist Hoe 140 (Hoechst-140: H-D-Arg 0 -Arg 1 -Pro 2 -Hyp 3 -Gly 4 -Thi 5 -Ser 6 -D-Tic 7 -Oic 8 -Arg 9 -OH) adopts a β-turn type II‘ about D-Tic 7 -Oic 8 in water/ SDS-micelles, in agreement with the important role for the C-terminal turn in the interaction with the B2 receptor.…”