Publication details
Molecular Dynamics Simulations on Cyclin Dependent Kinases 2 and 5. Contribution to Designing New Inhibitors and Understanding Mechanism of Activation/Inhibition
| Authors | |
|---|---|
| Year of publication | 2007 |
| Type | Article in Proceedings |
| Conference | Modeling Interaction in Biomolecules III |
| MU Faculty or unit | |
| Citation | |
| Field | Biophysics |
| Keywords | molecular dynamics cyclin dependent kinase |
| Description | We will show in this paper how molecular dynamics simulations can provide important information even if they cover very short period of time (ns). Subject of the study will be CDK-2 and CDK-5 enzymes, members of the family of Cyclin-dependent kinases (CDKs) that control the progression of the cell cycle and participate in a subset of apoptosis programs [1]. The first part will be focused on solvation while the other one to the mechanism of activation/inhibition. The interactions between the protein and the solvent were analyzed and protein regions with a high density of water molecules as well as tightly bound water molecules were determined [2] by using MD simulations [3]. A number of water molecules that were in longer contact with the protein were identified and compared with X-ray crystallography data [4]. We will show in the lecture how tracing tightly bound water molecules can be used in drug design. MD simulations are also used to help explaining structural implications on mechanism of activation and inhibition by phosphorylation. Simulations on CDK-2 and CDK-5 are compared to assess the differences and similarities between the two kinases in terms of (i) roscovitine binding, (ii) regulatory subunit association, (iii) conformational changes in the T-loop following CDK/regulatory subunit complex formation, and (iv) specificity in CDK/regulatory subunit recognition [5]. |
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