Insights on dynamic structural characteristics responsible for catalysis efficiency of protein disulfide isomerase through substrate interaction studies

Abstract

Abstract Protein Disulfide Isomerase (PDI) dynamic behaviour upon substrate interaction is discussed for structural characteristics investigation. Two different Peptide substrates hydrophobicity and disulfide interaction are chosen. The molecular docking is done by Discovery Studios 3.1 and HADDOCK v2.2, followed by molecular dynamics studies done by GROMACS 5.0.5 (AMBER force filed), and finally, protein domain motion is analysed by DynDom, which gives detailed insights on possible conformation changes in PDI while encountering a substrate. The analysis of obtained points out that, each peptide substrate displayed a unique set of interaction patterns and secondary structural elements fluctuations in PDI. Substrate binding made the C-terminal half of the molecule (b’ and a’ domain) rigid and the N-terminal half (b and a domain) flexible. PDI-Peptide complexes provide key insights into PDI with substrate interaction. b’ domain makes adjustments to the original conformation for stable PDI-Substrate complexes. This triggers disarray in the conformation of the entire protein. The results exposed the structural mechanism through which the reduced form of PDI undergoes metamorphosis into oxidized form by connecting two renowned crystal structures.

Keywords

• Protein disulfide isomerase
• Molecular docking
• Molecular dynamics simulation
• Peptide interaction
• Secondary structure transition
• Domain motion