6my2

Publication Abstract from PubMed

The cross-strand disulfides (CSDs) found in beta-hairpin antimicrobial peptides (beta-AMPs) show a unique disulfide geometry that is characterized by unusual torsion angles and a short Calpha-Calpha distance. While the sequence and disulfide bond connectivity of disulfide-rich peptides is well studied, much less is known about the disulfide geometry found in CSDs and their role in the stability of beta-AMPs. To address this, we solved the nuclear magnetic resonance (NMR) structure of the beta-AMP gomesin (Gm) at 278, 298, and 310 K, examined the disulfide bond geometry of over 800 disulfide-rich peptides, and carried out extensive molecular dynamics (MD) simulation of the peptides Gm and protegrin. The NMR data suggests Calpha-Calpha distances characteristic for CSDs are independent of temperature. Analysis of disulfide-rich peptides from the Protein Data Bank revealed that right-handed and left-handed rotamers are equally likely in CSDs. The previously reported preference for right-handed rotamers was likely biased by restricting the analysis to peptides and proteins solved using X-ray crystallography. Furthermore, data from MD simulations showed that the short Calpha-Calpha distance is critical for the stability of these peptides. The unique disulfide geometry of CSDs poses a challenge to biomolecular force fields and to retain the stability of beta-hairpin fold over long simulation times, restraints on the torsion angles might be required.

The unusual conformation of cross-strand disulfide bonds is critical to the stability of beta-hairpin peptides.,Deplazes E, Chin YK, King GF, Mancera RL Proteins. 2019 Oct 7. doi: 10.1002/prot.25828. PMID:31589791^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.