Self-assembling peptide-based nanotubes are among the most investigated bioactive compounds as a result of their numerous potential applications as novel biomaterials. To support rational bottom-up design of such artificial nanosystems, here we investigate structural and energetic properties of various sheet-derived nanotubes. We carried out high level quantum chemical calculations on large models, composed of up to 32 amino acids, and characterized structures from extended β-sheets to the molecular framework of β-barrel proteins. Surprisingly, enzyme-resistant nonnatural β-peptides have an affinity to form nanotubes that is remarkably higher than that of natural α-peptides. We analyzed the stability of both systems depending on (i) parallel or antiparallel orientation, (ii) the number of peptide strands, and (iii) the formed hydrogen bond pattern. Applicability is outlined by investigating guest molecules in the tubes. It is hoped that the structural and energetic data presented here will be effectively used in the design of novel peptide nanosystems.