Theoretical analysis of somatostatin receptor 5 with antagonists and agonists for the treatment of neuroendocrine tumors.
We report on SSTR5 receptor modeling and its interaction with reported antagonist and agonist molecules. Modeling of the SSTR5 receptor was carried out using multiple templates with the aim of improving the precision of the generated models. The selective SSTR5 antagonists, agonists and native somatostatin SRIF-14 were employed to propose the binding site of SSTR5 and to identify the critical residues involved in the interaction of the receptor with other molecules. Residues Q2.63, D3.32, Q3.36, C186, Y7.34 and Y7.42 were found to be highly significant for their strong interaction with the receptor. SSTR5 antagonists were utilized to perform a 3D quantitative structure-activity relationship study. A comparative molecular field analysis (CoMFA) was conducted using two different alignment schemes, namely the ligand-based and receptor-based alignment methods. The best statistical results were obtained for ligand-based ([Formula: see text], [Formula: see text] = 0.988, noc = 4) and receptor-guided methods (docked mode 1:[Formula: see text], [Formula: see text], noc = 5), (docked mode 2:[Formula: see text] = 0.555, [Formula: see text], noc = 5). Based on CoMFA contour maps, an electropositive substitution at [Formula: see text], [Formula: see text] and [Formula: see text] position and bulky group at [Formula: see text] position are important in enhancing molecular activity.
Department of Bioinformatics, School of Bioengineering, SRM University, SRM Nagar, Kattankulathur, Chennai, 603203, India.|Molecular Modelling Lab, Department of Genetic Engineering, School of Bioengineering, SRM University, SRM Nagar, Kattankulathur, Chennai, 603203, India.
Santhosh Kumar
SK
Nagarajan
Department of Bioinformatics, School of Bioengineering, SRM University, SRM Nagar, Kattankulathur, Chennai, 603203, India.|Molecular Modelling Lab, Department of Genetic Engineering, School of Bioengineering, SRM University, SRM Nagar, Kattankulathur, Chennai, 603203, India.
Sathya
S
Babu
Molecular Modelling Lab, Department of Genetic Engineering, School of Bioengineering, SRM University, SRM Nagar, Kattankulathur, Chennai, 603203, India. thiru.murthyunom@gmail.com.|Department of Genetic Engineering, School of Bioengineering, SRM University, SRM Nagar, Kattankulathur, Chennai, 603203, India. thiru.murthyunom@gmail.com.
Thirumurthy
T
Madhavan
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites; D006801:Humans; D062105:Molecular Docking Simulation; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011487:Protein Conformation; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D000970:Antineoplastic Agents; D010880:Piperidines; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5
3D QSAR; CoMFA; Comparative modeling; Docking; GPCR; SSTR5; Somatostatin