Drug design of cyclin-dependent kinase 2 inhibitor for melanoma from traditional Chinese medicine.

Hsin-Chieh Tang,Calvin Yu-Chian Chen

doi:10.1155/2014/798742

Abstract

One has found an important cell cycle controller. This guard can decide the cell cycle toward proliferation or quiescence. Cyclin-dependent kinase 2 (CDK2) is a unique target among the CDK family in melanoma therapy. We attempted to find out TCM compounds from TCM Database@Taiwan that have the ability to inhibit the activity of CDK2 by systems biology. We selected Tetrahydropalmatine, Reserpiline, and (+)-Corydaline as the candidates by docking and screening results for further survey. We utilized support vector machine (SVM), multiple linear regression (MLR) models and Bayesian network for validation of predicted activity. By overall analysis of docking results, predicted activity, and molecular dynamics (MD) simulation, we could conclude that Tetrahydropalmatine, Reserpiline, and (+)-Corydaline had better binding affinity than the control. All of them had the ability to inhibit the activity of CDK2 and might have the opportunity to be applied in melanoma therapy.

Highlights

One has discovered an important cell cycle controller
All the regions for key residues (Lys33 to Asp145) of Cyclindependent kinase 2 (CDK2) protein recorded in the literature did not locate at the disordered region
We could prove that the 3D structure of CDK2 (PDB ID: 1URW) was reliable (Figure 1)

Summary

Introduction

One has discovered an important cell cycle controller. This gatekeeper can decide the cell cycle toward proliferation or quiescence [1]. The cell cycle means division and duplication of the cells. The process can consist of interphase and mitotic (M) phase. Normal cell cycle follows the ordinary steps, but cancer cells grow without regulation. The rate of progress in cell cycle is decided by cyclins and cyclin-dependent kinases (CDKs). Entering of each phase is controlled by specific cyclin-CDK complex. CDK is like the engine in a car, and cyclin is like the gearbox. Cyclin E-CDK2 complex guides the process from G1 to S phase, while cyclin

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