Vol 11, Issue 2, 2018 Online - 2455-3891 Print - 0974-2441 MOLECULAR DOCKING OF AMITRIPTYLINE TO CERULOPLASMIN, RETINOL-BINDING PROTEIN, AND SERUM ALBUMIN RAMCHANDER MERUGU 1 , KALPANA V SINGH 2 * 1 Department of Biochemistry, University College of Science, Mahatma Gandhi University, Nalgonda, Telangana, India. 2 Department of Chemistry and Pharmaceutical Chemistry, Government Madhav Science Postgraduate College, Ujjain, Madhya Pradesh, India. Email: singhkalpana297@gmail.com Received: 22 August 2017, Revised and Accepted: 07 November 2017 ABSTRACT Objective: A drug’s efficiency depends on the binding capacity of the drug with the particular plasma protein. The less bound drug can be easily diffused through cell membranes. The present study deals with in silico studies of amitriptyline binding to three plasma proteins human ceruloplasmin (HCP), cellular retinol-binding protein (CRBP), and human serum albumin (HSA) and tries to establish the binding capacity behavior with the frontier molecular orbital approach. Methods: Amitriptyline is selected as legend and docked with three plasma proteins HCP, HCP PDB ID 1KCW, CRBP PDB ID 5LJC, and HSA. Docking calculations were carried out using docking server. frontier molecular orbital calculations are performed through web-based computational chemistry interface WEBMO version 17.0.012e using server Buchhner.chem.hope.edu. on computational engine MOPAC. Results: HCP and HSA predominantly show polar and hydrophobic interactions, whereas CRBP forms hydrogen bond apart from polar and hydrophobic interactions. Favorable values of inhibition constant, Ki, is obtained which is equal to 1.13 µM for CRBP, 6.00 µM for HCP, and 2.00 µM for has. Conclusion: A studies prove that amitriptyline can bind to all three plasma proteins, namely, HCP, CRBP, and HSA. Amitriptyline binds to an HSA and HCP through polar and hydrophobic interactions while weak electrostatic interactions felicitate diffusion of amitriptyline through the plasma membrane. Comparatively, strong hydrogen bond in CRBP may make the bound drug to be released at a slow rate. Strong binding of amitriptyline to CRBP is also evident from the least value of inhibition constant, Ki, which is equal to 1.13 µM for CRBP, 6.00 µM for HCP, and 2.00 µM for has. Keywords: Human ceruloplasmin, Retinol-binding protein, Human serum albumin, Amitriptyline. INTRODUCTION Human ceruloplasmin (HCP), (1KCW) is a member of the multicopper oxidase family of enzymes [1]. It was first isolated in 1944 [2] and has a molecular weight of some 132 kDa, being comprised of a single polypeptide chain of 1046 amino-acid residues with a carbohydrate content of between 7% and 8% [3]. The first X-ray structural study of HCP was reported in 1996 [4]. Copper is required for a wide variety of enzymatic reactions taking place in living cells [5-9]. CP physically interacts with transferrin, and it acts as a ferroxidase and is thought to mediate efflux of iron from cells, [10-12]. Cp does play a role in the transfer of Fe (II) to blood plasma transferring from some cells-like hepatocytes [13-15]. The arrangements of the trinuclear center and the mononuclear copper ion are similar to that of laccase and ascorbate oxidase [16-19]. Cellular retinol-binding protein (CRBP) appears to have several roles, including (1) delivering retinol to specific binding sites within the nucleus and (2) participating in the transepithelial movement of retinol across certain blood-organ barriers. Vitamin A is transported to the tissues in the form of retinol bound to RBP in a 1:1 complex and is largely regulated by the turnover rates of RBP [20]. Plasma RBP has 93% sensitivity for predicting marginal Vitamin A status [21]. Human serum albumin (HSA), is the most abundant protein in plasma, which is a main modulator of fluid distribution between body compartments [ 22-23]. HSA acts as a main carrier for fatty acids, affecting pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the antioxidant capacity of human plasma, and displays (pseudo-) enzymatic properties [24-29]. HSA is a valuable biomarker of many diseases [30-32] with potential applications as implantable biomaterials, surgical adhesives, sealants, and fusion proteins [33-35]. Albumin functions primarily as a carrier protein for different biomolecules. Mutations in this gene on chromosome 4 result in various anomalous proteins. Plasma proteins serve many functions including transport of drugs, lipids, hormones, vitamins, and minerals in the circulatory system. Serum Albumin accounts for 55% of plasma proteinsand most drugs screen for serum albumin only. Hence, in the present study, binding of the drug amitriptyline to other plasma proteins was investigated along with albumen. Docking technique used in the in silico studies predicts the binding of one molecule to the other through preferential orientations of the molecules. Different parameters such as free energy of binding, polar and hydrophobic interactions, and formation of hydrogen bond are identified during docking, and in silico studies are used extensively for studying the docking behavior [36,37]. METHODS Amitriptyline is selected as legend and docked with three plasma proteins HCP, HCP PDB ID 1KCW, CRBP PDB ID 5LJC, and HSA. Docking calculations were carried out using docking Server [38]. Gasteiger partial charges are added to the ligand atoms by the server during docking, non-polar hydrogen atoms are merged, and rotatable bonds are defined. As per server notification, AutoDock tools [39] are used for adding essential hydrogen atoms, Kollman united atom type charges, and solvation parameters. Autogrid program [39] generated affinity grid maps of × Å and 0.375 Å. AutoDock parameter set- and distance-dependent dielectric functions are used in the calculation of van der Waals and electrostatic terms, respectively. Lamarckian genetic algorithm and the Solis and Wets local search methods [40] are used for performing docking simulations. Initial position, © 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.v11i2.22721 Research Article