Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin

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dc.citation.articleNumber753en_US
dc.citation.journalTitleFrontiers in Molecular Biosciencesen_US
dc.citation.volumeNumber8en_US
dc.contributor.authorNde, Julesen_US
dc.contributor.authorZhang, Pengzhien_US
dc.contributor.authorEzerski, Jacob C.en_US
dc.contributor.authorLu, Weien_US
dc.contributor.authorKnapp, Kaitlinen_US
dc.contributor.authorWolynes, Peter G.en_US
dc.contributor.authorCheung, Margaret S.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2021-09-21T15:37:50Zen_US
dc.date.available2021-09-21T15:37:50Zen_US
dc.date.issued2021en_US
dc.description.abstractCalmodulin (CaM) is a calcium-binding protein that transduces signals to downstream proteins through target binding upon calcium binding in a time-dependent manner. Understanding the target binding process that tunes CaM’s affinity for the calcium ions (Ca2+), or vice versa, may provide insight into how Ca2+-CaM selects its target binding proteins. However, modeling of Ca2+-CaM in molecular simulations is challenging because of the gross structural changes in its central linker regions while the two lobes are relatively rigid due to tight binding of the Ca2+ to the calcium-binding loops where the loop forms a pentagonal bipyramidal coordination geometry with Ca2+. This feature that underlies the reciprocal relation between Ca2+ binding and target binding of CaM, however, has yet to be considered in the structural modeling. Here, we presented a coarse-grained model based on the Associative memory, Water mediated, Structure, and Energy Model (AWSEM) protein force field, to investigate the salient features of CaM. Particularly, we optimized the force field of CaM and that of Ca2+ ions by using its coordination chemistry in the calcium-binding loops to match with experimental observations. We presented a “community model” of CaM that is capable of sampling various conformations of CaM, incorporating various calcium-binding states, and carrying the memory of binding with various targets, which sets the foundation of the reciprocal relation of target binding and Ca2+ binding in future studies.en_US
dc.identifier.citationNde, Jules, Zhang, Pengzhi, Ezerski, Jacob C., et al.. "Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin." <i>Frontiers in Molecular Biosciences,</i> 8, (2021) Frontiers: https://doi.org/10.3389/fmolb.2021.661322.en_US
dc.identifier.digitalfmolb-08-661322en_US
dc.identifier.doihttps://doi.org/10.3389/fmolb.2021.661322en_US
dc.identifier.urihttps://hdl.handle.net/1911/111385en_US
dc.language.isoengen_US
dc.publisherFrontiersen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleCoarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulinen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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