Homology modeling and virtual screening studies of FGF-7 protein—a structure-based approach to design new molecules against tumor angiogenesis

• Published in: Journal of chemical biology Vol. 9; no. 3; pp. 69 - 78
• Main Authors: Vadija, Rajender, Mustyala, Kiran Kumar, Nambigari, Navaneetha, Dulapalli, Ramasree, Dumpati, Rama Krishna, Ramatenki, Vishwanath, Vellanki, Santhi Prada, Vuruputuri, Uma
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2016; Springer Nature B.V
• Subjects: Amino acids; Angiogenesis; Biochemistry; Biological and Medical Physics; Biophysics; Cancer; Cell Biology; Chemistry; Chemistry and Materials Science; Computer applications; Docking; Fibroblast growth factor 7; Growth factors; Homology; Hydrophobicity; Keratinocyte growth factor; Ligands; Molecular chains; Molecular structure; Original; Original Article; Pharmacology; Pharmacology/Toxicology; Physical Chemistry; Piperazine; Protein structure; Proteins; Residues; Screening; Therapeutic applications; Tumors; Virtual screening; Angiogenesis; FGF-7; Protein–protein docking; ADME
• ISSN: 1864-6158; 1864-6166
• DOI: 10.1007/s12154-016-0152-x

Keratinocyte growth factor (KGF) protein is a member of the fibroblast growth factor (FGF) family, which is also known as FGF-7. The FGF-7 plays an important role in tumor angiogenesis. In the present work, FGF-7 is treated as a potential therapeutic target to prevent angiogenesis in cancerous tissue. Computational techniques are applied to evaluate and validate the 3D structure of FGF-7 protein. The active site region of the FGF-7 protein is identified based on hydrophobicity calculations using CASTp and Q-site Finder active site prediction tools. The protein–protein docking study of FGF-7 with its natural receptor FGFR2b is carried out to confirm the active site region in FGF-7. The amino acid residues Asp34, Arg67, Glu116, and Thr194 in FGF-7 interact with the receptor protein (FGFR2b). A grid is generated at the active site region of FGF-7 using Glide module of Schrödinger suite. Subsequently, a virtual screening study is carried out at the active site using small molecular structural databases to identify the ligand molecules. The binding interactions of the ligand molecules, with piperazine moiety as a pharmacophore, are observed at Arg67 and Glu149 residues of the FGF-7 protein. The identified ligand molecules against the FGF-7 protein show permissible pharmacokinetic properties (ADME). The ligand molecules with good docking scores and satisfactory pharmacokinetic properties are prioritized and identified as novel ligands for the FGF-7 protein in cancer therapy.