• Soni Singh Department of Biotechnology and Life Sciences, Mangalayatan University, Aligarh, Uttar Pradesh, India.
  • Alok Jha Department of Biotechnology and Life Sciences, Mangalayatan University, Aligarh, Uttar Pradesh, India.



5-Hydroxytryptamine2a receptor, Homology modeling, G Protein-coupled receptors, Transmembrane protein, Model comparison


Objective: Structural characterization of 5-hydroxytryptamine (5-HT)2A receptor in homo sapiens using in silico method.

Methods: In silico approach has particularly providing a realistic representation needed to understand the fundamental molecular structure of a serotonin receptor. The structure has been generated using Swiss model, Modeller 9.14, Phyre2, and Geno three-dimensional, which was visualized using PyMol, and validated by Procheck and ERRAT analysis along with the values of different secondary structures mapping to diverse sections of the Ramachandran plot.

Results: We compared all different models. Further structural analysis suggested that the structure of 5-HT2A is a monomer with 18 alpha helices, seven beta sheets, and one disulfide bridge. There is no signal peptide region in the protein sequence. The structure contains mostly polar and aromatic amino acid as suggested by using hydropathy plot. However, in both partitioning systems bilayer to water and water to bilayer, there are some hydropathy predicted segments, which are also transmembrane segments. Finally, the pore features, including diameter profile, size, and shape, were determined by porewalker, and the shape of the pore was found to be UDSD.

Conclusion: This study suggested that 5-HT2A receptor interaction with its natural ligand serotonin and other inhibitor compounds would further additional information about G protein-coupled receptors. The 5-HT2A receptor could be an important target for therapeutics development.


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Remigio GJ. The Neurophysiology and Behavioral Pharmacology of Memory Enhancement and Memory Deficits in the Dentate Gyrus (Doctoral Dissertation, The University of Utah); 2017.

Leopoldo M, Lacivita E, Berardi F, Perrone R, Hedlund PB. Serotonin 5-HT7 receptor agents: Structure-activity relationships and potential therapeutic applications in central nervous system disorders. Pharmacol Ther 2011;129:120-48.

Katritch V, Cherezov V, Stevens RC. Structure-function of the G protein-coupled receptor superfamily. Annu Rev Pharmacol Toxicol 2013;53:531-56.

Peters JA, Kelley SP, Dunlop JI, Kirkness EF, Hales TG, Lambert JJ. The 5-hydroxytryptamine Type 3 (5-HT3) receptor reveals a novel determinant of single-channel conductance. Biochem Soc Trans 2004;32:547-52.

Raote I, Bhattacharya A, Panicker MM. Serotonin 2A (5-HT2A) receptor function: Ligand-dependent mechanisms and pathways. Serotonin Receptors in Neurobiology. Boca Raton: CRC Press; 2007. p. 1-17.

Zhang G, Stackman RW Jr. The role of serotonin 5-HT2A receptors in memory and cognition. Front Pharmacol 2015;6:225.

Dhonnchadha BÃ, Ripoll N, Clénet F, Hascoët M, Bourin M. Implication of 5-HT 2 receptor subtypes in the mechanism of action of antidepressants in the four plates test. Psychopharmacology 2005;179:418-29.

Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, et al. SWISS-MODEL: Modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 2014;42:W252-8.

Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ. The Phyre2 web portal for protein modeling, prediction and analysis. Nature Protocols 2015;10:845-58.

Combet C, Jambon M, Deleage G, Geourjon C. Geno3D: Automatic comparative molecular modelling of protein. Bioinformatics 2002;18:213-4.

Lovell SC, Davis IW, Arendall WB, de Bakker PI, Word JM, Prisant MG, et al. Structure validation by Cα geometry: ϕ, ψ and Cβ deviation. Proteins Struct Funct Bioinforma 2003;50:437-50.

Laskowski RA, MacArthur MW, Moss D, Thornton JM. PROCHECK: A program to check the stereo chemical quality of protein structures. J Appl Cryst 1993;26:283-91.

Laskowski RA, Chistyakov VV, Thornton JM. PDBsum more: New summaries and analyses of the known 3D structures of proteins and nucleic acids. Nucleic Acids 2005;33:D266-8.

Chen Y, Capponi S, Zhu L, Gellenbeck P, Freites JA, White SH, et al. YidC insertase of Escherichia coli: Water accessibility and membrane shaping. Structure 2017;25:1403-14.

Pellegrini-Calace M, Maiwald T, Thornton JM. Pore-walker: A novel tool for the identification and characterization of transmembrane protein channels from their three-dimensional structure. PLoS Comput Biol 2009;5:1-16.

Yang J, Roy A, Zhang Y. Protein-ligand binding site recognition using complementary binding-specific substructure comparison and sequence profile alignment. Bioinformatics 2013;29:2588-95.

Porollo A, Meller J. Prediction-based fingerprints of protein-protein interactions. Proteins 2007;66:630-45.

Bhattacharya D, Nowotny J, Cao R, Cheng J. 3D refine: An interactive web server for efficient protein structure refinement. Nucleic Acids Res 2016;44:W406-9.



How to Cite

Singh, S., and A. Jha. “STRUCTURAL CHARACTERISATION OF 5-HYDROXYTRYPTAMINE2A RECEPTOR IN HOMO SAPIENS BY IN - SILICO METHOD”. Asian Journal of Pharmaceutical and Clinical Research, vol. 11, no. 14, July 2018, pp. 81-85, doi:10.22159/ajpcr.2018.v11s2.28588.



Original Article(s)