Toward a better understanding of the interaction between somatostatin receptor 2 and its ligands: a structural characterization study using molecular dynamics and conceptual density functional theory

Abstract

This study is a part of the extensive research intending to provide the structural insights on somatostatin and its receptor. Herein, we have studied the structural complexity involved in the binding of somatostatin receptor 2 (SSTR2) with its agonists and antagonist. A 3D QSAR study based on comparative molecular field analysis and comparative molecular similarity analysis (CoMSIA) discerned that a SSTR2 ligand with electronegative, less-bulkier, and hydrogen atom donating/accepting substitutions is important for their biological activity. A conceptual density functional theory (DFT) study was followed to study the chemical behavior of the ligands based on the molecular descriptors derived using the Fukui’s molecular orbital theory. We have performed molecular dynamics simulations of receptor–ligand complexes for 100 ns to analyze the dynamic stability of the backbone Cα atoms of the receptor and strength and approachability of the receptor–ligand complex. The findings of this study could be efficacious in the further studies understanding intricate structural features of the somatostatin receptors and in discovering novel subtype-specific ligands with higher affinity.

Communicated by Ramaswamy H. Sarma

Keywords:

• somatostatin
• SSTR2
• DFT
• molecular dynamics
• CoMFA
• CoMSIA

Acknowledgements

The authors would like to thank SRM Institute of Science and Technology for providing the high-performance computer clustering system which helped in carrying out this study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research did not receive any special grant from funding agencies in the public, commercial or not-for-profit sectors.