Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin
Calmodulin (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...
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doaj-14dbb85fa2ec4d6caddb0b7b15c956452021-08-24T12:25:15ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-08-01810.3389/fmolb.2021.661322661322Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-CalmodulinJules Nde0Jules Nde1Pengzhi Zhang2Jacob C. Ezerski3Wei Lu4Kaitlin Knapp5Peter G. Wolynes6Margaret S. Cheung7Margaret S. Cheung8Department of Physics, University of Houston, Houston, TX, United StatesCenter for Theoretical Biological Physics, Rice University, Houston, TX, United StatesDepartment of Physics, University of Houston, Houston, TX, United StatesDepartment of Physics, University of Houston, Houston, TX, United StatesCenter for Theoretical Biological Physics, Rice University, Houston, TX, United StatesCenter for Theoretical Biological Physics, Rice University, Houston, TX, United StatesCenter for Theoretical Biological Physics, Rice University, Houston, TX, United StatesDepartment of Physics, University of Houston, Houston, TX, United StatesCenter for Theoretical Biological Physics, Rice University, Houston, TX, United StatesCalmodulin (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.https://www.frontiersin.org/articles/10.3389/fmolb.2021.661322/fullcalmodulin dynamicscalcium-binding proteinconformational changesintrinsic disorderAWSEMcommunity model |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jules Nde Jules Nde Pengzhi Zhang Jacob C. Ezerski Wei Lu Kaitlin Knapp Peter G. Wolynes Margaret S. Cheung Margaret S. Cheung |
spellingShingle |
Jules Nde Jules Nde Pengzhi Zhang Jacob C. Ezerski Wei Lu Kaitlin Knapp Peter G. Wolynes Margaret S. Cheung Margaret S. Cheung Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin Frontiers in Molecular Biosciences calmodulin dynamics calcium-binding protein conformational changes intrinsic disorder AWSEM community model |
author_facet |
Jules Nde Jules Nde Pengzhi Zhang Jacob C. Ezerski Wei Lu Kaitlin Knapp Peter G. Wolynes Margaret S. Cheung Margaret S. Cheung |
author_sort |
Jules Nde |
title |
Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin |
title_short |
Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin |
title_full |
Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin |
title_fullStr |
Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin |
title_full_unstemmed |
Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin |
title_sort |
coarse-grained modeling and molecular dynamics simulations of ca2+-calmodulin |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Biosciences |
issn |
2296-889X |
publishDate |
2021-08-01 |
description |
Calmodulin (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. |
topic |
calmodulin dynamics calcium-binding protein conformational changes intrinsic disorder AWSEM community model |
url |
https://www.frontiersin.org/articles/10.3389/fmolb.2021.661322/full |
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