Effects of thioamide substitutions on the conformation and stability of α- and 310-helices

Abstract

Thiopeptides, formed by replacing the amide oxygen atom with a sp2 sulfur atom, are useful in protein engineering and drug design because they confer resistance to enzymatic degradation and are predicted to be more rigid. This report describes our free molecular dynamics simulations with explicit water and free energy calculations on the effects of thio substitutions on the conformation of α-helices, 310-helices, and their relative stability. The most prominent structural effect of thio substitution is the increase in the hydrogen bond distance from 2.1 Å for normal peptides to 2.7 Å for thiopeptides. To accommodate for the longer C=S···H-N hydrogen bond, the (φ, ψ) dihedral angles of the α-..