Design of novel lead molecules against RhoG protein as cancer target - a computational study.
Cancer is a class of diseases characterized by uncontrolled cell growth. Every year more than 2 million people are affected by the disease. Rho family proteins are actively involved in cytoskeleton regulation. Over-expression of Rho family proteins show oncogenic activity and promote cancer progression. In the present work RhoG protein is considered as novel target of cancer. It is a member of Rho family and Rac subfamily protein, which plays pivotal role in regulation of microtubule formation, cell migration and contributes in cancer progression. In order to understand the binding interaction between RhoG protein and the DH domain of Ephexin-4 protein, the 3D structure of RhoG was evaluated and Molecular Dynamic Simulations was performed to stabilize the structure. The 3D structure of RhoG protein was validated and active site identified using standard computational protocols. Protein-protein docking of RhoG with Ephexin-4 was done to understand binding interactions and the active site structure. Virtual screening was carried out with ligand databases against the active site of RhoG protein. The efficiency of virtual screening is analysed with enrichment factor and area under curve values. The binding free energy of docked complexes was calculated using prime MM-GBSA module. The SASA, FOSA, FISA, PISA and PSA values of ligands were carried out. New ligands with high docking score, glide energy and acceptable ADME properties were prioritized as potential inhibitors of RhoG protein.
a Department of Chemistry , University College of Science, Osmania University , Tarnaka, Hyderabad 500007 , Telangana , India.
Thirupathi
T
Dasari
a Department of Chemistry , University College of Science, Osmania University , Tarnaka, Hyderabad 500007 , Telangana , India.
Bhargavi
B
Kondagari
a Department of Chemistry , University College of Science, Osmania University , Tarnaka, Hyderabad 500007 , Telangana , India.
Ramasree
R
Dulapalli
a Department of Chemistry , University College of Science, Osmania University , Tarnaka, Hyderabad 500007 , Telangana , India.
Aboubakr Haredi
AH
Abdelmonsef
a Department of Chemistry , University College of Science, Osmania University , Tarnaka, Hyderabad 500007 , Telangana , India.
Thirupathi
T
Mukkera
a Department of Chemistry , University College of Science, Osmania University , Tarnaka, Hyderabad 500007 , Telangana , India.
Lavanya Souda
LS
Padmarao
b Department of Chemistry , University College of Science, Osmania University , Saifabad, Hyderabad 500004 , Telangana , India.
Vasavi
V
Malkhed
a Department of Chemistry , University College of Science, Osmania University , Tarnaka, Hyderabad 500007 , Telangana , India.
Uma
U
Vuruputuri
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D015195:Drug Design; D055808:Drug Discovery; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D012372:ROC Curve; D012997:Solvents; D013329:Structure-Activity Relationship; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*
D000970:Antineoplastic Agents; D008024:Ligands; D012997:Solvents; D020741:rho GTP-Binding Proteins
homology modelling; molecular dynamics; prime MM-GBSA; protein–protein docking; virtual screening