Structural Modeling and Conformational Analysis of Aromatic Polypeptoid Models Confined to Different Environmental Conditions

Abstract

Conformations of achiral and chiral aromatic homopolypeptoids of Nphe, Nspe and Nrpe were studied by quantum mechanics and molecular dynamics approaches. The amide bond geometry in model peptoids Ac-X-NMe2 could be both cis and trans and the Nphe peptoids adopted degenerate conformations of opposite handedness with Φ, Ψ values of ~ ± 120o, ± 150o with trans amide bond geometry. This degeneracy was lifted with increase in chain length; in favor of the structure with Φ = -120o, Ψ = -150o. Polypeptoids of Nspe and Nrpe with and without protecting groups populated states with Φ, Ψ values of ~ 110o, 155o & -110o, -165o respectively with trans amide bond geometry. Simulation studies in water revealed that with protecting groups peptoid Ac-(Nspe/Nrpe)5-NMe2 populated with cis amide bond geometry in PP type I and inverse PP type I helices respectively due to interactions between the solvent molecules and carbonyl oxygens of the backbone. Without protecting groups these polypeptoids populated poly-Lproline type II conformations. In DMSO these peptoids were shown to populate in PP type-I and inverse PP type-I helices and without protecting groups they could be realized in PP type-I as well as inverse PP type-I conformation whereas the peptoid -Nrpe6-NH2 could be realized in inverse PP type-I conformation. Analysis of simulation results as a function of time ruled out amide bond inter-conversions between cis and trans geometry. Hence, like polyproline peptoids can also be exploited as molecular spacers.