title: Assisted peptide folding by surface pattern recognition.
abstract: Natively disordered proteins belong to a unique class of biomolecules whose function is related to their flexibility and their ability to adopt desired conformations upon binding to substrates. In some cases these proteins can bind multiple partners, which can lead to distinct structures and promiscuity in functions. In other words, the capacity to recognize molecular patterns on the substrate is often essential for the folding and function of intrinsically disordered proteins. Biomolecular pattern recognition is extremely relevant both in vivo (e.g., for oligomerization, immune response, induced folding, substrate binding, and molecular switches) and in vitro (e.g., for biosensing, catalysis, chromatography, and implantation). Here, we use a minimalist computational model system to investigate how polar/nonpolar patterns on a surface can induce the folding of an otherwise unstructured peptide. We show that a model peptide that exists in the bulk as a molten globular state consisting of many interconverting structures can fold into either a helix-coil-helix or an extended helix structure in the presence of a complementary designed patterned surface at low hydrophobicity (3.7%) or a uniform surface at high hydrophobicity (50%). However, we find that a carefully chosen surface pattern can bind to and catalyze the folding of a natively unfolded protein much more readily or effectively than a surface with a noncomplementary or uniform distribution of hydrophobic residues.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, California, USA.
authors.forename: Zhuoyun
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Jewett
authors.forename: Silvan
authors.initials: S
authors.lastname: Kuttimalai
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bellesia
authors.forename: S
authors.initials: S
authors.lastname: Gnanakaran
authors.forename: Joan-Emma
authors.initials: JE
authors.lastname: Shea
mesh_terms: D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013499:Surface Properties
chemical_list: D010455:Peptides