TY  - JOUR
AU  - Nguyen, Tin Trung
AU  - Tran, Duy Phuoc
AU  - Huy, Pham Dinh Quoc
AU  - Hoang, Zung
AU  - Carloni, Paolo
AU  - Van Pham, Phuc
AU  - Nguyen, Chuong
AU  - Li, Mai Suan
TI  - Ligand binding to anti-cancer target CD44 investigated by molecular simulations
JO  - Journal of molecular modeling
VL  - 22
IS  - 7
SN  - 0948-5023
CY  - Berlin
PB  - Springer
M1  - FZJ-2016-05799
SP  - 165
PY  - 2016
AB  - CD44 is a cell-surface glycoprotein and receptor for hyaluronan, one of the major components of the tumor extracellular matrix. There is evidence that the interaction between CD44 and hyaluronan promotes breast cancer metastasis. Recently, the molecule F-19848A was shown to inhibit hyaluronan binding to receptor CD44 in a cell-based assay. In this study, we investigated the mechanism and energetics of F-19848A binding to CD44 using molecular simulation. Using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) method, we obtained the binding free energy and inhibition constant of the complex. The van der Waals (vdW) interaction and the extended portion of F-19848A play key roles in the binding affinity. We screened natural products from a traditional Chinese medicine database to search for CD44 inhibitors. From combining pharmaceutical requirements with docking and molecular dynamics simulations, we found ten compounds that are potentially better or equal to the F-19848A ligand at binding to CD44 receptor. Therefore, we have identified new candidates of CD44 inhibitors, based on molecular simulation, which may be effective small molecules for the therapy of breast cancer.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000379014700020
C6  - pmid:27342250
DO  - DOI:10.1007/s00894-016-3029-6
UR  - https://juser.fz-juelich.de/record/820505
ER  -