Publication Cover
Molecular Physics
An International Journal at the Interface Between Chemistry and Physics
Volume 117, 2019 - Issue 17: 58th Sanibel Symposium Proceedings
106
Views
4
CrossRef citations to date
0
Altmetric
58th Sanibel Symposium

Theoretical study of conformational transition of CDK4 by association of cyclin D3

, , &
Pages 2355-2361 | Received 30 Apr 2018, Accepted 05 Dec 2018, Published online: 03 Jan 2019
 

ABSTRACT

We present coarse-grained simulations to investigate folding and association of cyclin-dependent kinase 4 (CDK4) with cyclin D3. In our simulations, the Gō-like model and our coarse-grained model are applied to describe intramolecular and intermolecular interaction of protein molecules, respectively. We investigate conformational stability of each state of CDK4 with/without association to cyclin D3 on a single basin potential with reference to each state of CDK4. The results of simulations for the native CDK4 with cyclin D3 are consistent with an experimental observation. The open CDK4 may associate to cyclin D3 on a different interface from cyclin D3-native CDK4 complex structure. If the open CDK4 associates to cyclin D3, the open CDK4 can slightly fold and become smaller, suggesting an unfolded intermediate. After a double-basin potential with reference to the native and open states of CDK4 is given, the open CDK4 associated with cyclin D3 can smoothly shift to the native CDK4. We propose a structure of a potential candidate of an unfolded intermediate during activation of CDK4.

GRAPHICAL ABSTRACT

Acknowledgements

The calculations were partly performed at the Research Center for Computational Science, Okazaki, Japan and the Center for Computational Sciences, University of Tsukuba, Tsukuba, Japan.

Disclosure statement

No potential conflict of interest was reported by the authors.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.