Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0043985
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dc.titleStapled BH3 Peptides against MCL-1: Mechanism and Design Using Atomistic Simulations
dc.contributor.authorJoseph, T.L.
dc.contributor.authorLane, D.P.
dc.contributor.authorVerma, C.S.
dc.date.accessioned2014-10-27T08:40:14Z
dc.date.available2014-10-27T08:40:14Z
dc.date.issued2012-08-31
dc.identifier.citationJoseph, T.L., Lane, D.P., Verma, C.S. (2012-08-31). Stapled BH3 Peptides against MCL-1: Mechanism and Design Using Atomistic Simulations. PLoS ONE 7 (8) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0043985
dc.identifier.issn19326203
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/101719
dc.description.abstractAtomistic simulations of a set of stapled alpha helical peptides derived from the BH3 helix of MCL-1 (Stewart et al. (2010) Nat Chem Biol 6: 595-601) complexed to a fragment (residues 172-320) of MCL-1 revealed that the highest affinity is achieved when the staples engage the surface of MCL-1 as has also been demonstrated for p53-MDM2 (Joseph et al. (2010) Cell Cycle 9: 4560-4568; Baek et al. (2012) J Am Chem Soc 134: 103-106). Affinity is also modulated by the ability of the staples to pre-organize the peptides as helices. Molecular dynamics simulations of these stapled BH3 peptides were carried out followed by determination of the energies of interactions using MM/GBSA methods. These show that the location of the staple is a key determinant of a good binding stapled peptide from a bad binder. The good binder derives binding affinity from interactions between the hydrophobic staple and a hydrophobic patch on MCL-1. The position of the staple was varied, guiding the design of new stapled peptides with higher affinities. © 2012 Joseph et al.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1371/journal.pone.0043985
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1371/journal.pone.0043985
dc.description.sourcetitlePLoS ONE
dc.description.volume7
dc.description.issue8
dc.description.page-
dc.identifier.isiut000308221300039
dc.published.statePublished
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