title: Characterization of folding cores in the cyclophilin A-cyclosporin A complex.
abstract: Determining the folding core of a protein yields information about its folding process and dynamics. The experimental procedures for identifying the amino acids that make up the folding core include hydrogen-deuterium exchange and Φ-value analysis and can be expensive and time consuming. Because of this, there is a desire to improve upon existing methods for determining protein folding cores theoretically. We have obtained HDX data for the complex of cyclophilin A with the immunosuppressant cyclosporin A. We compare these data, as well as literature values for uncomplexed cyclophilin A, to theoretical predictions using a combination of rigidity analysis and coarse-grained simulations of protein motion. We find that in this case, the most specific prediction of folding cores comes from a combined approach that models the rigidity of the protein using the first software suite and the dynamics of the protein using the froda tool.
authors: MOAC Doctoral Training Centre, University of Warwick, Coventry, United Kingdom; Institute for Advanced Study, University of Warwick, Coventry, United Kingdom. Electronic address: jack.heal@bristol.ac.uk.
authors: Jack W
authors: JW
authors: Heal
authors: Department of Chemistry, University of Bath, Bath, United Kingdom.
authors: Stephen A
authors: SA
authors: Wells
authors: Department of Chemistry, University of Warwick, Coventry, United Kingdom.
authors: Claudia A
authors: CA
authors: Blindauer
authors: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors: Robert B
authors: RB
authors: Freedman
authors: Centre for Scientific Computing, University of Warwick, Coventry, United Kingdom; Department of Physics, University of Warwick, Coventry, United Kingdom.
authors: Rudolf A
authors: RA
authors: Römer
mesh_terms: D000595:Amino Acid Sequence; D021984:Cyclophilin A / Q000737:chemistry* / Q000378:metabolism; D016572:Cyclosporine / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D016572:Cyclosporine; D021984:Cyclophilin A