title: Effects of knot type in the folding of topologically complex lattice proteins.
abstract: The folding properties of a protein whose native structure contains a 52 knot are investigated by means of extensive Monte Carlo simulations of a simple lattice model and compared with those of a 31 knot. A 52 knot embedded in the native structure enhances the kinetic stability of the carrier lattice protein in a way that is clearly more pronounced than in the case of the 31 knot. However, this happens at the expense of a severe loss in folding efficiency, an observation that is consistent with the relative abundance of 31 and 52 knots in the Protein Data Bank. The folding mechanism of the 52 knot shares with that of the 31 knot the occurrence of a threading movement of the chain terminus that lays closer to the knotted core. However, co-concomitant knotting and folding in the 52 knot occurs with negligible probability, in sharp contrast to what is observed for the 31 knot. The study of several single point mutations highlights the importance in the folding of knotted proteins of the so-called structural mutations (i.e., energetic perturbations of native interactions between residues that are critical for knotting but not for folding). On the other hand, the present study predicts that mutations that perturb the folding transition state may significantly enhance the kinetic stability of knotted proteins provided they involve residues located within the knotted core.
authors.affiliation: Centro de Física da Matéria Condensada and Departamento de Física, Faculdade de Ciências, Universidade de Lisboa, Av. Prof. Gama Pinto 2, 1649-003 Lisboa, Portugal.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Soler
authors.affiliation: Centro de Física da Matéria Condensada and Departamento de Física, Faculdade de Ciências, Universidade de Lisboa, Av. Prof. Gama Pinto 2, 1649-003 Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Nunes
authors.affiliation: Centro de Física da Matéria Condensada and Departamento de Física, Faculdade de Ciências, Universidade de Lisboa, Av. Prof. Gama Pinto 2, 1649-003 Lisboa, Portugal.
authors.forename: Patrícia F N
authors.initials: PF
authors.lastname: Faísca
mesh_terms: D018360:Crystallography, X-Ray; D030562:Databases, Protein; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D017096:Prion Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics
chemical_list: D011506:Proteins