Ligand binding to anti-cancer target CD44 investigated by molecular simulations

 http://repository.vnu.edu.vn/handle/VNU_123/27361

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 be-tween CD44 and hyaluronan promotes breast cancer metasta-sis.

Recently, the molecule F-19848A was shown to inhibit hyaluronan binding to receptor CD44 in a cell-based assay. In this study, we investigated themechanism 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 ener-gy 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 require-ments 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 inhib-itors, based on molecular simulation, which may be effective small molecules for the therapy of breast cancer.

Title:	Ligand binding to anti-cancer target CD44 investigated by molecular simulations
Authors:	Nguyen, Tin Trung Tran, Duy Phuoc Pham, Dinh Quoc Huy
Keywords:	Breast cancer Traditional Chinesemedicine Steeredmolecular dynamics Hyaluronan CD44.F-19848A
Issue Date:	2016
Publisher:	H. : ĐHQGHN
Citation:	ISIKNOWLEDGE
Abstract:	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 be-tween CD44 and hyaluronan promotes breast cancer metasta-sis. Recently, the molecule F-19848A was shown to inhibit hyaluronan binding to receptor CD44 in a cell-based assay. In this study, we investigated themechanism 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 ener-gy 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 require-ments 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 inhib-itors, based on molecular simulation, which may be effective small molecules for the therapy of breast cancer.
Description:	JOURNAL OF MOLECULAR MODELING Volume: 22 Issue: 7 ; 14 p. ; TNS06422
URI:	http://repository.vnu.edu.vn/handle/VNU_123/27361
Appears in Collections:	Bài báo của ĐHQGHN trong Web of Science