Glide Docking, Autodock, Binding Free Energy and Drug-Likeness Studies for Prediction of Potential Inhibitors of Cyclin-Dependent Kinase 14 Protein in Wnt Signaling Pathway
Revanth Bathula, Narasimha Muddagoni, Goverdhan Lanka, Mahender Dasari, Sarita Rajender Potlapally, J Ferlay, M Colombet, I Soerjomataram, C Mathers, D Parkin, M Pieros, A Znaor, F Bray, D Wood, J Endicott, M Peyressatre, C Prvel, M Pellerano, M Morris, P Kaldis, M Pagano, F Shu, S Lv, Y Qin, X Ma, X Wang, X Peng, Y Luo, B Xu, X -E.; Sun, J Wu, G Davidson, J Shen, Y.-L Huang, Y Su, E Karaulanov, K Bartscherer, C Hassler, P Stannek, M Boutros, C Niehrs, H Baarsma, M Knigshoff, L Arce, N Yokoyama, M Waterman, X Gu, Y Wang, H Wang, Q Ni, C Zhang, J Zhu, W Huang, P Xu, G Mao, S Yang, K Boras-Granic, J Wysolmerski, M.-H Liu, S.-M Shi, K Li, E.-Q Chen, L Zheng, Z Zhou, Z He, J Zhu, C Liu, F Liu, Y Wang, M Zhu, J Ou-Yang, L.-H Huang, X.-X Sun, W Zhang, R Liu, C Tang, Q Xi, S Lu, W Chen, L Zhu, J Cheng, Y Chen, W Wang, J Zhong, Y Deng, L Yang, J Zhu, H Huang, Q Yang, J Cai, Q Wang, J Zhu, M Shao, J Xiao, J Cao, X Gu, S Zhang, Y Wang, A Morgat, T Lombardot
Abstract
Cyclin-dependent kinase 14 plays an essential role in multiple cancers. Cyclin-dependent kinase 14 is a serine/threonine kinase and is a member of the cell division cycle 2(cdc2) related protein kinase family, which plays a key role in promoting Wnt signaling pathway of the cell cycle and its overexpression causes various human cancers. The 3D structure of cyclin-dependent kinase 14 was built using the homology-based modeling technique. The generated model is optimized by NAMD-VMD software. The quality of stabilized CDK14 protein was checked using Ramachandran plot and ProSA servers. The potential binding site region was recognized using SiteMap and manual correlation techniques from literature studies. The virtual screening was performed with the TOSLab database of 27253 output molecules against CDK14 protein using Glide docking to assess novel chemical entities. Their binding energies were calculated from PrimeMMGSA and AutoDock. The novel lead molecules have been prioritized based on efficient binding energies (from AutoDock and PrimeMMGBSA), better glide scores, good bioavailability, and acceptable ADME properties. Thus, these are considered as CDK14 protein inhibitors for cancer therapeutics.