Comparative study of SP[6-11] and its analogs using simulated annealing

In this study we compared the steric structures of the bioactive part of substance P (SP[6-11]) and its analogs (NY3460 and pHOPA-SP5). The molecular dynamics-simulated annealing method was used to explore the conformational space, and the structural differences and similarities of these molecules were identified. For the three peptides, the conformational distributions were represented in Ramachandran density plots. The occurring secondary structural elements of the investigated molecules were identified, namely alpha-Helix, type III beta-Turn, gamma-Turn, and inverse gamma-Turn. For SP[6-11] and its two analogs, different intramolecular interactions (H-bonds between the main-chain atoms, aromatic-aromatic interactions, and amino-aromatic interactions) that can stabilize the various conformations of the three peptides were investigated. Detailed examination of these intramolecular interactions revealed that H-bonds between the main-chain atoms are relevant in the determination and stabilization of the conformer structures of the peptides, while the aromatic-aromatic interactions do not play an important stabilizing role. Furthermore, in the conformers of NY3460 and pHOPA-SP5, different types of amino-aromatic interactions were identified that contribute to the formation of the various structures of these peptides. For all three molecules, the orientations of the side chains were investigated and the rotamer populations were determined.