Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-017-15930-4
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dc.titleCharacterizing the conformational landscape of MDM2-binding p53 peptides using Molecular Dynamics simulations
dc.contributor.authorYadahalli, S
dc.contributor.authorLi, J
dc.contributor.authorLane, D.P
dc.contributor.authorGosavi, S
dc.contributor.authorVerma, C.S
dc.date.accessioned2020-09-04T03:30:38Z
dc.date.available2020-09-04T03:30:38Z
dc.date.issued2017
dc.identifier.citationYadahalli, S, Li, J, Lane, D.P, Gosavi, S, Verma, C.S (2017). Characterizing the conformational landscape of MDM2-binding p53 peptides using Molecular Dynamics simulations. Scientific Reports 7 (1) : 15600. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-017-15930-4
dc.identifier.issn2045-2322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174385
dc.description.abstractThe conformational landscapes of p53 peptide variants and phage derived peptide (12/1) variants, all known to bind to MDM2, are studied using hamiltonian replica exchange molecular dynamics simulations. Complementing earlier observations, the current study suggests that the p53 peptides largely follow the 'conformational selection' paradigm in their recognition of and complexation by MDM2 while the 12/1 peptides likely undergo some element of conformational selection but are mostly driven by 'binding induced folding'. This hypothesis is further supported by pulling simulations that pull the peptides away from their bound states with MDM2. This data extends the earlier mechanisms proposed to rationalize the entropically driven binding of the p53 set and the enthalpically driven binding of the 12/1 set. Using our hypothesis, we suggest mutations to the 12/1 peptide that increase its helicity in simulations and may, in turn, shift the binding towards conformational selection. In summary, understanding the conformational landscapes of the MDM2-binding peptides may suggest new peptide designs with bespoke binding mechanisms. © 2017 The Author(s).
dc.publisherNature Publishing Group
dc.sourceUnpaywall 20200831
dc.subjectMDM2 protein, human
dc.subjectpeptide
dc.subjectprotein binding
dc.subjectprotein MDM2
dc.subjectprotein p53
dc.subjectTP53 protein, human
dc.subjectbinding site
dc.subjectchemistry
dc.subjectgenetics
dc.subjecthuman
dc.subjectmolecular dynamics
dc.subjectmutation
dc.subjectprotein conformation
dc.subjectprotein secondary structure
dc.subjectthermodynamics
dc.subjectX ray crystallography
dc.subjectBinding Sites
dc.subjectCrystallography, X-Ray
dc.subjectHumans
dc.subjectMolecular Dynamics Simulation
dc.subjectMutation
dc.subjectPeptides
dc.subjectProtein Binding
dc.subjectProtein Conformation
dc.subjectProtein Structure, Secondary
dc.subjectProto-Oncogene Proteins c-mdm2
dc.subjectThermodynamics
dc.subjectTumor Suppressor Protein p53
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentBIOLOGY (NU)
dc.description.doi10.1038/s41598-017-15930-4
dc.description.sourcetitleScientific Reports
dc.description.volume7
dc.description.issue1
dc.description.page15600
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