caa a22 4500 467938695 CHVBK 20180406153005.0 cr unu---uuuuu 170328e20060601xx s 000 0 eng 10.1007/s10822-006-9081-z doi (NATIONALLICENCE)springer-10.1007/s10822-006-9081-z Molecular dynamics simulations on the inhibition of Cyclin-Dependent Kinases 2 and 5 in the presence of activators [Elektronische Daten] [Bing Zhang, Vincent Tan, Kian Lim, Tong Tay] Interests in CDK2 and CDK5 have stemmed mainly from their association with cancer and neuronal migration or differentiation related diseases and the need to design selective inhibitors for these kinases. Molecular dynamics (MD) simulations have not only become a viable approach to drug design because of advances in computer technology but are increasingly an integral part of drug discovery processes. It is common in MD simulations of inhibitor/CDK complexes to exclude the activator of the CDKs in the structural models to keep computational time tractable. In this paper, we present simulation results of CDK2 and CDK5 with roscovitine using models with and without their activators (cyclinA and p25). While p25 was found to induce slight changes in CDK5, the calculations support that cyclinA leads to significant conformational changes near the active site of CDK2. This suggests that detailed and structure-based inhibitor design targeted at these CDKs should employ activator-included models of the kinases. Comparisons between P/CDK2/cyclinA/roscovitine and CDK5/p25/roscovitine complexes reveal differences in the conformations of the glutamine around the active sites, which may be exploited to find highly selective inhibitors with respect to CDK2 and CDK5. Springer Science+Business Media, LLC, 2006 Cyclin-dependent kinase nationallicence Drug design nationallicence Inhibitors nationallicence Molecular dynamics nationallicence Selectivity nationallicence (CDK) : Cyclin-Dependent Kinase nationallicence P/CDK2/cyclinA/roscovitine : Thr160−phosphated/CDK2/cyclinA/roscovitine nationallicence Zhang Bing Nanoscience and Nanotechnolgy Initiative, National University of Singapore, S117576, Singapore, Singapore aut Tan Vincent Nanoscience and Nanotechnolgy Initiative, National University of Singapore, S117576, Singapore, Singapore aut Lim Kian Nanoscience and Nanotechnolgy Initiative, National University of Singapore, S117576, Singapore, Singapore aut Tay Tong Nanoscience and Nanotechnolgy Initiative, National University of Singapore, S117576, Singapore, Singapore aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/6(2006-06-01), 395-404 0920-654X 20:6<395 2006 20 10822 https://doi.org/10.1007/s10822-006-9081-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9081-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Bing Nanoscience and Nanotechnolgy Initiative, National University of Singapore, S117576, Singapore, Singapore aut NATIONALLICENCE 700 1- Tan Vincent Nanoscience and Nanotechnolgy Initiative, National University of Singapore, S117576, Singapore, Singapore aut NATIONALLICENCE 700 1- Lim Kian Nanoscience and Nanotechnolgy Initiative, National University of Singapore, S117576, Singapore, Singapore aut NATIONALLICENCE 700 1- Tay Tong Nanoscience and Nanotechnolgy Initiative, National University of Singapore, S117576, Singapore, Singapore aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/6(2006-06-01), 395-404 0920-654X 20:6<395 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer