Mukt Shabd Journal ISSN NO : 2347-3150

IN SILICO MOLECULAR DOCKING OF VANILLIC ACID AGAINST APOPTOTIC PROTEINS

Senthil. J, Janaki Devi. V1, Padma Priya. V1 Ashok. K* and Babu. M*, *1Department of Microbiology and Biotechnology, Faculty of Arts and Science, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, India ABSTRACT

The present molecular docking study can be useful for the design and development of novel compound having better inhibitory activity against apoptotic proteins (Caspase-3 and Caspase-9). The docking scores were highest for Caspase-9 with 36.471 kcal/mol with the stronger interaction followed by Caspase-3 (36.9 kcal/mol) and the LogP, lower hydrogen bond counts, confirming the capability of the vanillic acid for binding at the active site of the receptor. The results clearly show that the molecular docking mechanism used to detect the novel anticancer inhibitor has been successfully obtained from a natural polyphenolic compound.

Keywords: Vanillic acid, Discovery Studio, Caspase-3 and Caspase-9

INTRODUCTION

Vanillic acid (4-hydroxy-3-methoxybenzoic acid) (VA) is a polyphenolic dihydroxybenzoic acid compound produced by secondary metabolism in plants and is widely used in the food industry as a flavoring, food additive and preservative and in pharmaceutical industries as analeptic drug (etamivan) (Fig. 1A and B). The pleasant vanilla scent is due to the molecular structure corresponding to the oxidative form of vanillin aldehyde (vanilla). VA can be found in many foods, including rice, wheat, mango, strawberries, sugar cane, herbs and spices, beer, wine, tea and juices [1-30].

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Fig. 1: Vanillic acid A- 2D structure and B-3D structure

Taking together, these findings suggest that vanillic acid has beneficial properties such as antimicrobial, hepatotoxicity, antioxidant, cardiovascular disease, hemorheological effects, neuroprotective effects and antihypertensive [31-36]. The objective of the study is to identify that apoptotic proteins fit to the domain and active sites, to assess the chemical and physical properties of the protein, to analyze the potentiality of the therapeutic agents in terms of their properties, to perform Docking of the proteins with a compound vanillin acid and to evaluate the compound docking and active site binding.

MATERIALS AND METHODS

Preparation of protein structure

Apoptotic protein structures of Caspase-3 (Fig. 2 and 3) and Caspase-9 (Fig. 4 and 5) were obtained from RCSB Protein Data Bank (http: //www. pdb. org). All water molecules were removed and on the final stage hydrogen atoms were added to the target protein molecule.

Caspase-3 (PDB ID 2DKO.A)

Gene: CASP3 Organism: Homo sapiens (Human) BLAST sequence

>sp|P42574|10-28

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SKSIKNLEPKIIHGSESMD FASTA sequence

>3KJF:B|PDBID|CHAIN|SEQUENCE SGVDDDMACHKIPVDADFLYAYSTAPGYYSWRNSKDGSWFIQSLCAMLKQYADKL EFMHILTRVNRKVATEFESFSFDAT FHAKKQIPCIVSMLTKELYFYHHHHHHHH

Fig. 2: 3D structure of Caspase-3

Fig. 3: Caspase-3 protein sequence chain view

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Caspase-9 (PDB ID 2AR9)

Gene: CASP9 Organism: Homo sapiens (Human) BLAST sequence

>sp|P55211|1-92 MDEADRRLLRRCRLRLVEELQVDQLWDALLSRELFRPHMIEDIQRAGSGSRRDQAR QLII DLETRGSQALPLFISCLEDTGQDMLASFLRTN FASTA sequence

>2AR9:A|PDBID|CHAIN|SEQUENCE MGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSS LHFMVEVKGDLTAKKMVLALLE LARQDHGALDCCVVVILSHGCQASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSL GGKPKLFFIQASGGEQKDHGFEV ASTSPEDESPGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPK SGSWYVETLDDIFEQWAHSE DLQSLLLRVANAVSVKGIYKQMPCIVSMLRKKLFFKTS

Fig. 4: 3D structure of Caspase-9

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Fig. 5: Caspase-9 protein sequence chain view

Preparation of ligand structure

ChemSketch, chemically intelligent drawing interface freeware developed by Advanced Chemistry Development, Inc., (http: //www. acdlabs. com).

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Physical and chemical properties of ligand were retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/8468.

The key results in a (Discovery Studio) docking log are the docked structures found at the end of each run, the energies of these docked structures and their similarities to each other.

RESULTS AND DISCUSSION

Fig. 6: Pharmacore model of vanillin acid against apoptotic proteins

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Fig. 7: Docked complex of vanillin against Caspase-3

Fig. 8: Docked complex of vanillin against Caspase-9

Table 1: Docking score of vanillin acid against apoptotic proteins

Name of the protein Ligand Lib docking score H-B KCal/mol Caspase-3 36.9 4 Caspase-9 Vanillin acid 36.471 3

To study the binding mode of Vanillin acid interaction with apoptotic protein, intermolecular flexible docking simulations were performed and. Energy values were calculated from the docked conformations of the protein‐inhibitor complexes. Docking studies yielded crucial information concerning the orientation of the inhibitors in the binding pocket of the target protein. Several potential inhibitors have been identified through the docking simulation. The binding affinity of the apoptotic proteins with the Vanillin acid was measured by kcal/mol. The docking scores were highest for Caspase-9 with 36.471 kcal/mol with the stronger interaction followed by Caspase-3 (36.9 kcal/mol.) as showed in the table 1 and Fig. 6, 7 and 8 Analysis of ligand binding interaction with the protein can be useful for new preventive and therapeutic drug for cancer. The results obtained from this study would be useful in both understanding the inhibitory mode as well as in rapidly and accurately predicting the activities of new inhibitors on the basis of docking scores.

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Moreover, the apoptosis induced by the vanillin acid is mitochondrial mediated pathway as shown in the figure 9.

Fig. 9: Apoptosis was mediated by mitochondrial pathway

For the first time, natural polyphenolic compound (Vanillin acid) is docked with apoptotic proteins, which can bind to the active site of the protein and interfere with its activity, thereby ensuring the anticancer activity of the vanillic acid. The docking study of the results showed that the vanillin acid tested could be bound to the apoptotic proteins. The results clearly show that the molecular docking mechanism used to detect the novel anticancer inhibitor has been successfully obtained from a natural polyphenolic compound.

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CONCLUSSION

In this study, the molecular docking was applied to explore the binding mechanism and to correlate its docking score with the activity of Vanillin acid. The results of our present study can be useful for the design and development of novel compound having better inhibitory activity against several type of cancer. These potential drug candidates can further be validated in wet lab studies for its proper function.

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