Simulation Study Of The Ribosomal Exit Tunnel On Protein Folding

Protein structure is complicated and its folding problem has always been hotresearched. An in-depth understanding of protein folding mechanism in vivo has greatsignificance to clarify pathogenic mechanism of protein misfolding and look for a cure.To study the role of ribosome exit tunnel in the early stage of protein foldingprocess, we build a pipeline model of cylinder and select multiple small protein as theresearch object, including the structures of SH3domain (PDB:2NUZ), death domain(PDB:1DGN), serine protease inhibitors (PDB:2CI2) and human immunodeficiencyvirus type1p6protein (PDB:2C55). All-atom molecular dynamics simulation has beencarried out to study their folding behavior in the tunnel. Research results show that earlyfolding in the tunnel can effectively promote the formation of protein secondary structure;Regardless of their native conformation as full of α-helix, full of β-sheet, α/β hybridstructure or disorder sequence, all of their early folding in the tunnel can rapidly form astable α-helix, and after the proteins in the tunnel are released into the free space, theycan quickly collapse and form local tertiary structure. The structures that have formedsecondary structure can still maintain a high level of stability, which has a positive effectin promoting their late folding, so theoretically it should be faster to the proteins’ nearnative states than their folding in completely free space. Secondly, the peptides thatcontain β-sheet in their native structures, their folding in the tunnel cannot form or canonly form a small amount of isolated beta-bridge. The α-helix have formed in the tunnelwill open in the later and refold into β-sheet structure. Finally, we also try to do somework to study the folding mechanism of disorder protein, and the mechanism oftemperature induced disorder protein folding remains to be further validation.