Vol 11, Special issue 2, 2018 Online - 2455-3891 Print - 0974-2441 STRUCTURAL CHARACTERISATION OF 5-HYDROXYTRYPTAMINE 2A RECEPTOR IN HOMO SAPIENS BY IN - SILICO METHOD SONI SINGH, ALOK JHA* Department of Biotechnology and Life Sciences, Mangalayatan University, Aligarh, Uttar Pradesh, India. Email: alok.gene@gmail.com Received: 19 March 2018, Revised and Accepted: 10 July 2018 ABSTRACT 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-HT 2A 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-HT 2A receptor interaction with its natural ligand serotonin and other inhibitor compounds would further additional information about G protein-coupled receptors. The 5-HT 2A receptor could be an important target for therapeutics development. Keywords: 5-Hydroxytryptamine 2a receptor, Homology modeling, G Protein-coupled receptors, Transmembrane protein, Model comparison. INTRODUCTION Serotonin 5-hydroxytryptamine (5-HT) is one of the neurotransmitters present at synapses of nerve cells. In the central nervous system (CNS), serotonin is mainly involved in the regulation of depression, anxiety, aggression, memory, appetite, cognition, sleep, emotion, perception, and consciousness [1]. The 5-HT receptors have been classified into 5-HT 1 –5HT 7 , and again they are divided into 12 different subpopulations. Some agonists and antagonists for subpopulations of 5-HT receptors are being developed by using different approaches. Still as far yet, to design and develop a specific inhibitor for 5-HT receptors with therapeutic potential is a challenge, although many agonists and antagonists have been suggested [2]. All serotonergic receptors come under the category of G-protein-coupled receptor (GPCR) superfamily [3] except 5-HT3 receptor. The 5-HT3 receptor is one of the ligand-gated ion channels and depends on the nicotinic acetylcholine receptor superfamily having cysteine-loop transmitter gate, and constitute of heteropentamers [4,5]. The 5-HT 2A receptor is mainly present in the prefrontal cortex of CNS, and they are present in that region of the brain, which is essential for learning and cognition. The activity of this receptor is linked to many neurological disorders and conditions such as schizophrenia and depression. [5]. The 5HT 2 receptors are subdivided into 5-HT 2A , 5-HT 2B , and 5-HT 2C receptors. 5-HT 2A receptors exhibit high sequence homology with other 5-HT receptors (78%). Phenylalkylamines (like (2,5-dimethyl- 4-bromoamphetamine) and (2,5-dimethoxy-4iodoamphetamine)) are well known agonists for 5-HT 2A [6]. There are so many drugs available to target this receptor. Although the receptor has been widely studied about multiple functions in the CNS, high level of this receptor has been studied in other parts of the body such as platelets, endothelial cells, and intestine (Fig. 1). METHODS Template selection and model building The protein sequence and information of 5-HT 2A were collected from the National Center of Biotechnology (NCBI), in FASTA format, with the accession number NP > AAH96839.1 5. The sequence length reported to be 471 amino acids. To search for homologous sequence of 5-HT 2A , BLASTP was performed against the nonredundant database of NCBI. Sequences are selected from the sequence similarity search based on the identity percentage (cutoff 95% identity). The 471 amino acid residue of 5-HT 2A receptor was subjected to BLASTP against the Protein Data Bank [7] to identify suitable template for comparative study of the protein structure for modeling.Further, the protein sequence was subjected to comparative homology modeling through Modeler 9.14, SWISS-MODEL Server [8], PHYRE2 server [9], and Geno three- dimensional (3D) server [10]. These modeling servers on the basis of their different algorithm provide 3D structure of 5-HT 2A structure for further study. Validation of generated model Finally, once the 3D structures were generated, evaluation of the structure and stereochemical analysis was performed using different types of validation tools. A study of backbone conformation of all models was evaluated by the analysis of Ramachandran plot using RAMPAGE program [11]. ERRAT tool finds the overall quality factor of the proteins. ERRAT plot gives statistics of the error in the structure for each residue in the 3D protein structure model. This process was repeated, until when most of the amino acid residues was shown below 95% cutoff [12]. © 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2018.v11s2.28588 Research Article Recent Trends in Biomedical Sciences-2018 (RTBS-2018)