title: How determinant is N-terminal to C-terminal coupling for protein folding?
abstract: This work investigates the role of N- to C- termini coupling in the folding transition of small, single domain proteins via extensive Monte Carlo simulations of both lattice and off-lattice models. The reported results provide compelling evidence that the existence of native interactions between the terminal regions of the polypeptide chain (i.e. termini coupling) is a major determinant of the height of the free energy barrier that separates the folded from the denatured state in a two-state folding transition, therefore being a critical modulator of protein folding rates and thermodynamic cooperativity. We further report that termini interactions are able to substantially modify the kinetic behavior dictated by the full set of native interactions. Indeed, a native structure of high contact order with "switched-off" termini-interactions actually folds faster than its circular permutant of lowest CO.
authors.affiliation: Centro de Física da Matéria Condensada and Departamento de Física, Faculdade de Ciências da Universidade de Lisboa, Portugal.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Krobath
authors.forename: Antonio
authors.initials: A
authors.lastname: Rey
authors.forename: Patrícia F N
authors.initials: PF
authors.lastname: Faísca
mesh_terms: D007700:Kinetics; D009010:Monte Carlo Method; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D011506:Proteins