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

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dc.citation.articleNumber753
dc.citation.journalTitleFrontiers in Molecular Biosciences
dc.citation.volumeNumber8
dc.contributor.authorNde, Jules
dc.contributor.authorZhang, Pengzhi
dc.contributor.authorEzerski, Jacob C.
dc.contributor.authorLu, Wei
dc.contributor.authorKnapp, Kaitlin
dc.contributor.authorWolynes, Peter G.
dc.contributor.authorCheung, Margaret S.
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2021-09-21T15:37:50Z
dc.date.available2021-09-21T15:37:50Z
dc.date.issued2021
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.
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.
dc.identifier.digitalfmolb-08-661322
dc.identifier.doihttps://doi.org/10.3389/fmolb.2021.661322
dc.identifier.urihttps://hdl.handle.net/1911/111385
dc.language.isoeng
dc.publisherFrontiers
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleCoarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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