Effects of tethering a multistate folding protein to a surface

• Published in: The Journal of chemical physics Vol. 134; no. 18; p. 185101
• Main Authors: Wei, Shuai, Knotts, 4th, Thomas A
• Format: Journal Article
• Language: English
• Published: United States 14-05-2011
• Subjects: Bacteriophage T4 - enzymology; Models, Molecular; Muramidase - chemistry; Protein Conformation; Protein Folding; Surface Properties
• ISSN: 1089-7690
• DOI: 10.1063/1.3589863

Protein/surface interactions are important in a variety of fields and devices, yet fundamental understanding of the relevant phenomena remains fragmented due to resolution limitations of experimental techniques. Molecular simulation has provided useful answers, but such studies have focused on proteins that fold through a two-state process. This study uses simulation to show how surfaces can affect proteins which fold through a multistate process by investigating the folding mechanism of lysozyme (PDB ID: 7LZM). The results demonstrate that in the bulk 7LZM folds through a process with four stable states: the folded state, the unfolded state, and two stable intermediates. The folding mechanism remains the same when the protein is tethered to a surface at most residues; however, in one case the folding mechanism changes in such a way as to eliminate one of the intermediates. An analysis of the molecular configurations shows that tethering at this site is advantageous for protein arrays because the active site is both presented to the bulk phase and stabilized. Taken as a whole, the results offer hope that rational design of protein arrays is possible once the behavior of the protein on the surface is ascertained.