title: Long range recognition and selection in IDPs: the interactions of the C-terminus of p53.
abstract: The C-terminal domain of p53 is an extensively studied IDP, interacting with different partners through multiple distinct conformations. To explore the interplay between preformed structural elements and intrinsic fluctuations in its folding and binding we combine extensive atomistic equilibrium and non-equilibrium simulations. We find that the free peptide segment rapidly interconverts between ordered and disordered states with significant populations of the conformations that are seen in the complexed states. The underlying global folding-binding landscape points to a synergistic mechanism in which recognition is dictated via long range electrostatic recognition which results in the formation of reactive structures as far away as 10 Å, and binding proceeds with the steering of selected conformations followed by induced folding at the target surface or within a close range.
authors.affiliation: Bioinformatics Institute (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671.
authors.forename: Srinivasaraghavan
authors.initials: S
authors.lastname: Kannan
authors.affiliation: p53 Laboratory (A*STAR), 8A Biomedical Grove, #06-04/05, Neuros/Immunos, Singapore 138648.
authors.forename: David P
authors.initials: DP
authors.lastname: Lane
authors.affiliation: Bioinformatics Institute (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671.|School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.|Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543.
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Verma
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D019925:Cyclin A / Q000737:chemistry*; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D064568:S100 Calcium Binding Protein beta Subunit / Q000737:chemistry*; D037761:Sirtuins / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
chemical_list: D019925:Cyclin A; D064267:Intrinsically Disordered Proteins; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D016159:Tumor Suppressor Protein p53; D037761:Sirtuins