Computational analysis of differential interactions between cyclins and CDKs.
Members of cyclin-dependent kinase (CDKs) family in complex with their cognate regulatory subunits, cyclins, have been implicated in the control of essential cellular activities. Recent gene-targeted knockout studies performed on different cyclin-CDK complexes opposes the ‘classical model’ of cell-c...
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| Format: | Final Year Project (FYP) |
| Language: | English |
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2010
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| Online Access: | http://hdl.handle.net/10356/38812 |
| _version_ | 1826121806388396032 |
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| author | See, Pui Fun. |
| author2 | Chandra Shekhar Verma |
| author_facet | Chandra Shekhar Verma See, Pui Fun. |
| author_sort | See, Pui Fun. |
| collection | NTU |
| description | Members of cyclin-dependent kinase (CDKs) family in complex with their cognate regulatory subunits, cyclins, have been implicated in the control of essential cellular activities. Recent gene-targeted knockout studies performed on different cyclin-CDK complexes opposes the ‘classical model’ of cell-cycle regulation. Moreover, structural studies have yet to demonstrate precisely the molecular mechanisms behind the selectivity of cyclins for a preferred subset of CDKs; with incomplete structural details concerning their interactions. To understand if selectivity does exist at the interface between multiple cyclin-CDKs complexes, the present work describes the molecular models for binary complexes of yet-to-be crystallized cyclin-CDK assemblies. Classically, cyclinA2 and cyclinE1 is found to complex with CDK2 while two D-type cyclins are found to complex with CDK4. With the aid of a priori interface predictions, data-driven docking study using HADDOCK was performed. Four structural models of cyclinA2-CDK4, cyclinE1-CDK4, cyclinD3-CDK2 and cyclinD1-CDK2 complexes were generated. Assessment of the models showed that cross-interactions may occur between cyclins and CDKs. Though the quality of binding could be attributed to the presence of specific subsets of inter-molecular contacts, a conserved core set of interactions were found at the interfaces. This suggests that the consensus view of selectivity of cyclins for a preferred subset of CDKs needs to be re-examined. |
| first_indexed | 2024-10-01T05:38:10Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/38812 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:38:10Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | ntu-10356/388122023-02-28T18:06:22Z Computational analysis of differential interactions between cyclins and CDKs. See, Pui Fun. Chandra Shekhar Verma School of Biological Sciences A*STAR Bioinformatics Institute DRNTU::Science::Biological sciences::Biomathematics Members of cyclin-dependent kinase (CDKs) family in complex with their cognate regulatory subunits, cyclins, have been implicated in the control of essential cellular activities. Recent gene-targeted knockout studies performed on different cyclin-CDK complexes opposes the ‘classical model’ of cell-cycle regulation. Moreover, structural studies have yet to demonstrate precisely the molecular mechanisms behind the selectivity of cyclins for a preferred subset of CDKs; with incomplete structural details concerning their interactions. To understand if selectivity does exist at the interface between multiple cyclin-CDKs complexes, the present work describes the molecular models for binary complexes of yet-to-be crystallized cyclin-CDK assemblies. Classically, cyclinA2 and cyclinE1 is found to complex with CDK2 while two D-type cyclins are found to complex with CDK4. With the aid of a priori interface predictions, data-driven docking study using HADDOCK was performed. Four structural models of cyclinA2-CDK4, cyclinE1-CDK4, cyclinD3-CDK2 and cyclinD1-CDK2 complexes were generated. Assessment of the models showed that cross-interactions may occur between cyclins and CDKs. Though the quality of binding could be attributed to the presence of specific subsets of inter-molecular contacts, a conserved core set of interactions were found at the interfaces. This suggests that the consensus view of selectivity of cyclins for a preferred subset of CDKs needs to be re-examined. Bachelor of Science in Biological Sciences 2010-05-19T02:56:04Z 2010-05-19T02:56:04Z 2010 2010 Final Year Project (FYP) http://hdl.handle.net/10356/38812 en Nanyang Technological University 32 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Biomathematics See, Pui Fun. Computational analysis of differential interactions between cyclins and CDKs. |
| title | Computational analysis of differential interactions between cyclins and CDKs. |
| title_full | Computational analysis of differential interactions between cyclins and CDKs. |
| title_fullStr | Computational analysis of differential interactions between cyclins and CDKs. |
| title_full_unstemmed | Computational analysis of differential interactions between cyclins and CDKs. |
| title_short | Computational analysis of differential interactions between cyclins and CDKs. |
| title_sort | computational analysis of differential interactions between cyclins and cdks |
| topic | DRNTU::Science::Biological sciences::Biomathematics |
| url | http://hdl.handle.net/10356/38812 |
| work_keys_str_mv | AT seepuifun computationalanalysisofdifferentialinteractionsbetweencyclinsandcdks |