Structural Studies of Predicted Ligand Binding Sites and Molecular Docking Analysis of Slc2a4 as a Therapeutic Target for the Treatment of Cancer

Abstract

Presently, many studies have focused on exploring in silico approaches in the identification and development of alternative therapy for the treatment and management of cancer. Solute carrier family-2-member-4-gene (Slc2a4) which encodes glucose transporter 4 protein (GLUT4), has been identified as a promising therapeutic target for cancer. Though Slc2a4 is known to play a major regulatory role in the pathophysiology of type 2 diabetes, emerging evidence suggests that successful pharmacological inhibition of this protein may lead to the development of a novel drug candidate for the treatment of cancer. In this study, Slc2a4 protein sequence was retrieved and analysed using in silico approaches, and we identified seven putative antimicrobial peptides (AMPs; RAB1-RAB7) as anti-cancer. The structures of the protein and AMPs were modelled using I-TASSER server, and the overall quality of the Slc2a4 model was validated using PROCHECK. Subsequently, the probable motifs and active site of the protein were forecasted. Also, the molecular interaction between the AMPs and Slc2a4 was ascertained using PatchDock. The result revealed that, all the AMPs are good Slc2a4 inhibitors with RAB1 having the highest binding affinity of 12,392 and binding energy of −39.13 kcal/mol. Hence, this study reveals that all the generated AMPs can serve as therapeutic drug in treating cancer by inhibiting Slc2a4 which is responsible for the production of energy for cancer cells during angiogenesis. This is the first report on AMPs as inhibitors of Slc2a4 for the treatment of cancer.

Homology Model and Docking-Based Virtual Screening for Ligands of Human Dyskerin as New Inhibitors of Telomerase for Cancer Treatment

“…Both processes converged in two models that were later analyzed by PROCHECK software, in order to check the stereochemical quality of the protein structure and analyze its overall and residue-by-residue geometry. The obtained results indicated that homology modeling presented appropriate quality parameters ( Figure 5 ) [ 12 ], with values similar to the ones reported in other very interesting works [ 29 , 30 ]. Given this, studies were continued with the homology model of hDKC1.…”

<p>Structural and Molecular Docking Analytical Studies of the Predicted Ligand Binding Sites of Cadherin-1 in Cancer Prognostics</p>

“…The predicted hydrophobic value of the AMPs was greater than 30% as anticipated for an ideal AMP and these values contributed significantly to their high binding potential to receptors and cells. 29 This work is in accordance with the work of Aruleba et al, 30 where AMPs were used to investigate the structural and predicted binding sites of Slc2a4 as a therapeutic target in the treatment of cancer.…”

Pemodelan Molekuler Peptida Bioaktif Laut sebagai Antikoagulan Alami terhadap Enzim Sitokrom P450 (CYP) 2C9

“…Jarak antara bagian permukaan makromolekul enzim dan molekul peptida bioaktif dibatasi dengan batas radius maksimum 4.0 Å. Studi penambatan molekuler ini menggunakan parameter dengan berdasar pada representasi bentuk molekul, bagian sisi aktif pengikatan makromolekul target, serta pemilihan dan penilaian. Studi penambatan molekuler ini juga dilakukan secara efisien tanpa adanya ikatan antar molekul yang bersifat rigid (Aruleba et al, 2018).…”