title: Interplay between native topology and non-native interactions in the folding of tethered proteins.
abstract: We assessed the interplay of native topology and non-native interactions on surface-tethered protein folding via extensive Monte Carlo simulations of a simple lattice model. In particular, we investigated the thermodynamics and kinetics of protein-like sequences enclosing different amounts of non-native interactions to protein energetics, and which were designed to fold to distinct native topologies. Our results show that the high-contact order (CO) structure renders a folding transition that is robust to (external) steric constraints and non-native interactions. On the other hand, the folding process of the simple low-CO topology can be easily hampered by the presence of a nearby chemically inert plane. In this case, if non-native interactions are highly conspicuous during folding they can actually drive chain collapse into a very native-like trapped state, which impedes the formation of the native structure. The analysis of folding kinetics reveals that the empirical correlation between folding rate and CO may not apply to surface-tethered protein folding. Indeed, results reported here show that depending on the native environment of the tethered chain terminus the folding rate of a low-CO topology can become so drastically small that the high-CO topology actually folds faster under the same conditions. We predict that complex topologies are more likely to conserve their bulk folding mechanism upon surface tethering.
authors.affiliation: Departamento de Física, Centro de Física da Matéria Condensada, Universidade de Lisboa, Av. Prof. Gama Pinto 2, 1649-003 Lisboa, Portugal. heinrich.krobath@gmx.at
authors.forename: Heinrich
authors.initials: H
authors.lastname: Krobath
authors.forename: Patrícia F N
authors.initials: PF
authors.lastname: Faísca
mesh_terms: D003198:Computer Simulation; D007700:Kinetics; D008958:Models, Molecular; D009010:Monte Carlo Method; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins