title: Molecular dynamics simulation on the conformational transition of the mad2 protein from the open to the closed state.
abstract: The Mad2 protein, with two distinct conformations of open- and closed-states, is a key player in the spindle checkpoint. The closed Mad2 state is more active than the open one. We carried out conventional and targeted molecular dynamics simulations for the two stable Mad2 states and their conformational transition to address the dynamical transition mechanism from the open to the closed state. The intermediate structure in the transition process shows exposure of the β6 strand and an increase of space around the binding sites of β6 strand due to the unfolding of the β7/8 sheet and movement of the β6/4/5 sheet close to the αC helix. Therefore, Mad2 binding to the Cdc20 protein in the spindle checkpoint is made possible. The interconversion between these two states might facilitate the functional activity of the Mad2 protein. Motion correlation analysis revealed the allosteric network between the β1 strand and β7/8 sheet via communication of the β5-αC loop and the β6/4/5 sheet in this transition process.
authors.affiliation: College of Chemistry, Beijing Normal University, 19 Xinjiekouwai Street, Beijing 100875, China. lichaoqun_210@163.com.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Chemistry, Zhengzhou University, Zhengzhou 450052, Henan, China. zhuyan@zzu.edu.cn.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: College of Chemistry, Beijing Normal University, 19 Xinjiekouwai Street, Beijing 100875, China. wangy@bnu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Chemistry, Beijing Normal University, 19 Xinjiekouwai Street, Beijing 100875, China. gjchen@bnu.edu.cn.
authors.forename: Guangju
authors.initials: G
authors.lastname: Chen
mesh_terms: D001665:Binding Sites; D064199:Cdc20 Proteins / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology*; D064246:Mad2 Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D008941:Spindle Apparatus
chemical_list: D064199:Cdc20 Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; C577488:CDC20 protein, human