An α → β transition underlies the first step of disease causing amyloidogenesis in many proteins. In view of this, many studies have been carried out using peptide models to characterize these secondary structural transitions. In this paper we show that an insertion/duplication mutant ‘L20’ of bacteriophage T4 lysozyme (M. Sagermann, W. A. Baase and B. W. Matthews, Proc. Natl. Acad. Sci. U.S.A., 1999, 96, 6078) displays an α → β transition. We performed molecular dynamics (MD) simulation of L20, using the GROMACS package of programs and united atom GROMOS 53a6 force field for a time period of 600 ns at 300 K, in explicit water. Our MD simulation demonstrated that the transition occurs in a duplicated α-helical region inserted tandemly at the N-terminus of the ‘parent’ helix. We show that a C-terminal β-sheet anchors the parent helix while the loosely held N-terminal loop in the duplicate region is vulnerable to solvent attack and thus undergoes an α → β transition. Main chain–solvent interactions were seen to stabilize the observed β-structure. Thus L20 serves as a good protein model for characterization of α → β transition in a full length protein.
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