TY - DATA T1 - Protein-Associated Cation Clusters in Aqueous Arginine Solutions and Their Effects on Protein Stability and Size PY - 2013/02/15 AU - Vincent Vagenende AU - Alvin X. Han AU - Monika Mueller AU - Bernhardt L. Trout UR - https://acs.figshare.com/articles/journal_contribution/Protein_Associated_Cation_Clusters_in_Aqueous_Arginine_Solutions_and_Their_Effects_on_Protein_Stability_and_Size/2442652 DO - 10.1021/cb300440x.s001 L4 - https://ndownloader.figshare.com/files/4085311 KW - cluster KW - Molecular dynamics simulations KW - arginine cations KW - protein surface KW - protein surface loci KW - Aqueous Arginine Solutions N2 - Arginine is one of the most prominent residues in protein interactions, and arginine hydrochloride is widely used as an additive in protein solutions because of its exceptional effects on protein association and folding. The molecular origins of arginine effects on protein processes remain, however, controversial, and little is known about the molecular interactions between arginine cations and protein surfaces in aqueous arginine solutions. In this study, we report a unique biochemical phenomenon whereby clusters of arginine cations (Arg+) are associated with a protein surface. The formation of protein-associated Arg+ clusters is initiated by Arg+ ions that associate with specific protein surface loci through cooperative interactions with protein guanidinium and carboxyl groups. Molecular dynamics simulations indicate that protein-associated Arg+ ions subsequently attract other Arg+ ions and form dynamic cation clusters that extend further than 10 Å from the protein surface. The effects of arginine on the thermal stability and size of lysozyme and ovalbumin are measured over a wide concentration range (0 to 2 M), and we find that the formation of protein-associated Arg+ clusters consistently explains the complex effects of arginine on protein stability and size. This study elucidates the molecular mechanisms and implications of cluster formation of Arg+ ions at a protein surface, and the findings of this study may be used to manipulate synthetic and biological systems through arginine-derived groups. ER -