title: Topology-based models and NMR structures in protein folding simulations.
abstract: Topology-based interaction potentials are simplified models that use the native contacts in the folded structure of a protein to define an energetically unfrustrated folding funnel. They have been widely used to analyze the folding transition and pathways of different proteins through computer simulations. Obviously, they need a reliable, experimentally determined folded structure to define the model interactions. In structures elucidated through NMR spectroscopy, a complex treatment of the raw experimental data usually provides a series of models, a set of different conformations compatible with the available experimental data. Here, we use an efficient coarse-grained simulation technique to independently consider the contact maps from every different NMR model in a protein whose structure has been resolved by the use of NMR spectroscopy. For lambda-Cro repressor, a homodimeric protein, we have analyzed its folding characteristics with a topology-based model. We have focused on the competition between the folding of the individual chains and their binding to form the final quaternary structure. From 20 different NMR models, we find a predominant three-state folding behavior, in agreement with experimental data on the folding pathway for this protein. Individual NMR models, however, show distinct characteristics, which are analyzed both at the level of the interplay between tertiary/quaternary structure formation and also regarding the thermal stability of the tertiary structure of every individual chain.
authors.affiliation: Departamento de Química Física I, Facultad de Ciencias Químicas, Universidad Complutense, E-28040 Madrid, Spain.
authors.forename: M Fernanda
authors.initials: MF
authors.lastname: Rey-Stolle
authors.forename: Marta
authors.initials: M
authors.lastname: Enciso
authors.forename: Antonio
authors.initials: A
authors.lastname: Rey
mesh_terms: D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D011487:Protein Conformation; D017510:Protein Folding; D012097:Repressor Proteins / Q000737:chemistry*; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry*
chemical_list: D012097:Repressor Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins