Assessment of the conformational profile of bombesin by computational methods

Abstract

In the present work, the results of a computational study aimed at assessing the conformational profile of bombesin are reported. The conformational space of the peptide was sampled by means of a 4 μs accelerated molecular dynamics simulation in water, using an explicit solvent model. The results were analyzed using Principal Component Analysis to get essential information on peptide fluctuations, along with cluster analysis to characterize different conformations in the sample. Analysis of the results suggests that the peptide adopts helical structures at the C-terminus that tend to unwind at the end of the peptide chain, since there are many structures exhibiting only two turns of a helix at the central segment of the peptide. In addition, the peptide also adopts hairpin turn structures at the N-terminus. Results of the simulation were confronted with available NMR results in a 2,2,2-trifluoroethanol/water (30% v/v) solution. Distances deduced form NOEs experiments only provide support to the presence of helical conformations that represent the most populated structures in the simulation. The absence of other conformations in the NMR experiments can be explained to be due to the α-helix enhancing nature of the solvent used in the experiments.