title: Protein folding: Vexing debates on a fundamental problem.
abstract: The folding of proteins has been at the heart of protein chemistry and biophysics ever since the pioneering experiments by the labs of Fred Richards and Christian Anfinsen. But, despite nearly 60 years of intense research, there are unresolved issues and a lively debate regarding some aspects of this fundamental problem. In this review we give a personal account on some key topics in the field: (i) the nature of the denatured state of a protein, (ii) nucleation sites in the folding reaction, and (iii) the time it takes for individual molecules to traverse the transition state.
authors.affiliation: Istituto Pasteur, Fondazione Cenci Bolognetti and Istituto di Biologia e Patologia Molecolari del CNR, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli" Sapienza, University of Rome, 00185 Rome, Italy; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom. Electronic address: Stefano.Gianni@uniroma1.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gianni
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-75123 Uppsala, Sweden. Electronic address: Per.Jemth@imbim.uu.se.
authors.forename: Per
authors.initials: P
authors.lastname: Jemth
mesh_terms: D009154:Mutation; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D011506:Proteins
keywords: Denatured state; Kinetics; Mutagenesis; Protein folding; Transition path time; Transition state