biostudies-literatureKrishna MMNIGMS NIH HHS1053-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC545867biostudies-literatureUnknown102(4)Essentially all proteins known to fold kinetically in a two-state manner have their N- and C-terminal secondary structural elements in contact, and the terminal elements often dock as part of the experimentally measurable initial folding step. Conversely, all N-C no-contact proteins studied so far fold by non-two-state kinetics. By comparison, about half of the single domain proteins in the Protein Data Bank have their N- and C-terminal elements in contact, more than expected on a random probability basis but not nearly enough to account for the bias in protein folding. Possible reasons for this bias relate to the mechanisms for initial protein folding, native state stability, and final turnover.Proceedings of the National Academy of Sciences of the United States of AmericaThe N-terminal to C-terminal motif in protein folding and function.PMC545867GM31847R01 GM031847Englander SWKrishna MMfalseThe N-terminal to C-terminal motif in protein folding and function.Essentially all proteins known to fold kinetically in a two-state manner have their N- and C-terminal secondary structural elements in contact, and the terminal elements often dock as part of the experimentally measurable initial folding step. Conversely, all N-C no-contact proteins studied so far fold by non-two-state kinetics. By comparison, about half of the single domain proteins in the Protein Data Bank have their N- and C-terminal elements in contact, more than expected on a random probability basis but not nearly enough to account for the bias in protein folding. Possible reasons for this bias relate to the mechanisms for initial protein folding, native state stability, and final turnover.2005-01-01T00:00:00Z2005 Jan2025-04-20T01:35:46.142Z2019-03-27T01:08:32ZS-EPMC5458671565711810.1073/pnas.0409114102