Conformational profile of bombesin assessed using different computational protocols

The present work involves the study of the conformational profile of bombesin using different computational procedures used to explore the configurational space based on molecular dynamics simulations. Specifically, the present study describes the effect of using Berendsen's versus Langevin's thermostat and on the other hand, the use of the multicanonical replica exchange molecular dynamics as compared to standard molecular dynamics. In these simulations the solvent was modeled using the Onufriev, Bashford and Case implementation of Generalized Born procedure. The detailed computational analysis agrees well with the aggregated information previously reported in the NMR study of the peptide in a mixture of trifluoroethanol/water. Present results show a clear preference for the peptide to attain a helical structure on the segment 6–14, with a tendency to adopt a α-helix at the C-terminus aligning the aromatic residues Trp8 and His12 together with Gln7, known to be important for peptide mediated activation. Finally, the three methodologies used in the present work yield similar structural results, although a detailed analysis reveals biases that need to be considered when performing this kind of studies.

Figure optionsDownload high-quality image (193 K)Download as PowerPoint slideResearch highlights▶ Demonstrates equivalent results within the sampling conditions of MD (200 ns) and REMD (100 ns) for sampling a 14-residue peptide. ▶ Using GB in its OBS implementation together with the AMBER ff96 provides results in agreement with NMR studies in TFE/water. ▶ The peptide exhibits a dual conformational behavior never described before. On the one hand, a clear tendency to exhibit a helix between residues 6 and 14, already observed in NMR studies. On the other, a trend to conserved the helix turn between Gly5 and Ala9. These results explain the known structure–activity studies known and opens the door to understand the affinity of the peptide to two different receptors: BB1 and BB2.