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European Journal of Applied Sciences – Vol. 11, No. 5
Publication Date: October 25, 2023
DOI:10.14738/aivp.115.15413
Ferrari, I. V., Gregorio, A. D., Fuggetta, M. P., & Ravagnan, G. (2023). PharmMapper Server and Molecular Docking Study Focusing
on Polydatin to Identify Potential Targets. European Journal of Applied Sciences, Vol - 11(5). 163-167.
Services for Science and Education – United Kingdom
PharmMapper Server and Molecular Docking Study Focusing on
Polydatin to Identify Potential Targets
Ivan Vito Ferrari
Institute of clinical physiology of CNR, Massa, Italy
Alex De Gregorio
Institute of Translational Pharmacology,
Consiglio Nazionale delle Ricerche, Rome, Italy
Maria Pia Fuggetta
Institute of Translational Pharmacology,
Consiglio Nazionale delle Ricerche, Rome, Italy
Giampietro Ravagnan
Institute of Translational Pharmacology,
Consiglio Nazionale delle Ricerche, Rome, Italy
ABSTRACT
In this short communication, we focused on the biological role of Polydatin through
two computerized analyzes (phamacophore study by PharmMapper server and
Molecular Docking by Autodock Vina with the Pyrx program). According to the best
normalized fit scores calculated by the PharmMapper database, Polydatin may be
attractive for the following potential targets: Triggering receptor expressed on
myeloid cells 1; Ephrin type-B receptor; Tyrosine protein kinase (HCK); ADP -ribose
pyrophosphatase; mitochondrial Putative ATP-dependent Clp protease proteolytic
subunit; Seprase and Caspase-3, ranked by normalized fit score in descending order
(0.9921 to 09812). All these potential targets calculated by PharmMapper server
are used to evaluate their role by the Docking method through Autodock Vina with
Polydatin. From the results of the binding energies of our docking approach, only
three potential targets play a key role with Polydatin, which are: the Trigger
receptor expressed on myelod cells, mitochondrial ADP -ribose pyrophospatase,
and Seprase (fibroblast activation protein). However, further computational
methods and in vitro and in vivo assays are required to confirm our preliminary
results.
Keywords: Polydatin, Pharmacophore, Autodock Vina, Molecular Docking, PharmMapper
INTRODUCTION
Computational biology is nowadays focused on the design and development of computer
models to represent and simulate biological systems and solve related problems. In recent
years, these disciplines have attracted increasing interest in the medical field [1].
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European Journal of Applied Sciences (EJAS) Vol. 11, Issue 5, October-2023
In biology and medicine, there are a number of computational methods aimed at reducing
experimental times and costs in drug delivery and discovery. Among the most studied methods
is Molecular Docking [2], a computational method required for structure-based virtual
screening to identify new molecular candidates for the development of new therapeutic
approaches. Another well- known investigation is Pharmacophore analysis [3], which is based
on the spatial arrangement of features essential for a molecule to interact with a specific target
receptor and is an alternative method to molecular docking to achieve this goal.
The focus of the present study was to use Autodock Vina to determine the best theorical binding
energies scores (kcal/mol) of Polydatin with various potential target proteins and receptors
[4]. Other computational methods well known nowadays are the study of drug similarity
assessment and ADMET (absorption, distribution, metabolism, excretion and toxicity)
prediction to investigate the pharmacokinetic and toxic properties of drugs and small
compounds [5].
In this short communication, we mainly focus on two classical methods as Pharmacophore and
Molecular Docking studies focused on the biological role of the natural compound named
Polydatin, a natural potent Polyphenol. Polydatin (PD), also called Piceid (3,4',5-
trihydroxystilbene-3-β-d-glucoside), is a glycosylated form Resveratrol with excellent
anticancer and antioxidant properties [6]. Many papers in the Literature reported that PD has
antioxidant, anti-free radical, and anti-inflammatory properties [6-8].
MATERIALS AND METHODS
PharmMapper Server (http://www.lilab-ecust.cn/)
It is an open-access web server for identifying potential targets (drugs, natural products, or
other newly discovered compounds with as yet unidentified binding targets) using the
Pharmacophore mapping approach. Thank you to the highly efficient and robust mapping
method, PharmMapper has a high throughput performance and can identify the potential
targets from the database within a few hours [9].
Target Receptor Preparation for Docking Analysis
The 3D structures investigated in this work are:
Tiggering receptor expressed on myeloid cells 1 (PDB 1Q8M); Ephrin type-B receptor 4 (PDB
2VWU); Tyrosine protein kinase (PDB 2HCK); mitochondrial ADP-ribose Pyrophosphatase
(PDB 1Q33);Seprase (PDB 1Z68); Caspase-3 (PDB 3DEJ). These targets are accurately prepared
by Chimera program: all hydrogens and Gasteiger charges were added by Chimera and finally
the structures were converted in PDBQT format.
Ligand Preparation Workflow for Docking Analysis
PD was taken from the PubChem Database (https://pubchem.ncbi.nlm.nih.gov/) in 3D
Conformer SDF and was processed by Chimera through MFF94 force field with Steepest Descent
Optimization Algorithm. All hydrogens and Gasteiger charges were added by Autodock Tools
and finally the structures were minimized and converted in PDBQT format.
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Ferrari, I. V., Gregorio, A. D., Fuggetta, M. P., & Ravagnan, G. (2023). PharmMapper Server and Molecular Docking Study Focusing on Polydatin to
Identify Potential Targets. European Journal of Applied Sciences, Vol - 11(5). 163-167.
URL: http://dx.doi.org/10.14738/aivp.115.15413
RESULTS AND DISCUSSION
PharmMapper Server
PharmMapper Server is a freely accessible web server designed to identify potential targets for
given small probe molecules (drugs, natural products, or other newly discovered compounds
with unidentified binding targets) using the Pharmacophore Mapping approach [9].
PharmMapper was used to test the potential target proteins for PD. This is one of the web
servers for potential drug targets identification via the large-scale reverse pharmacophore
mapping strategy. Drug target identification, which involves several different algorithms for
finding genes and proteins, is the first step in drug discovery. When 3D structures of the targets
are available, the problem of target identification is usually transferred to finding the best mode
of interaction between the potential target candidates and the small molecule probes.
Pharmacophore is the spatial arrangement of features essential for a molecule to interact with
a particular target receptor, and was applied as a preliminary evaluation of the target molecules
before molecular docking analysis. The best results from PharmMapper analyses are reported
in Table 1.
Table 1: Best Pharmacophore candidates of Polydatin, identified by PharmMapper
PDB ID Target name Normalized fit score
1Q8M Triggering Receptor 0.9921
2VWU Ephrin type-B receptor 4 0.9887
2HCK Tyrosine protein kinase 0.9877
1Q33 mithocondrial ADP-ribose pyrophospatase 0.9843
1Z68 Seprase 0.9843
3DEJ Caspase-3 0.9812
The characteristics of the selected targets are briefly reported below.
PDB 1Q8M (Crystal Structure of the Human Myeloid Cell Activating Receptor TREM-1):
Triggering receptors expressed on myeloid cells (TREM) are a family of recently discovered
receptors that play an important role in innate immuno responses, such as activation of
inflammatory responses and septic shock in response to microbially mediated infections.
PDB 2VWU (EphB4 Kinase Domain Inhibitor Complex):
The EphB4 is one of the Eph receptor family, the largest subgroup of tyrosine kinase receptors,
associated with angiogenesis, growth, and metastasis of tumors, making it a valuable and
attractive target for drug development for therapeutic applications.
PDB 2HCK (SRC FAMILY KINASE HCK-QUERCETIN COMPLEX):
Hematopoetic cell kinase (HCK) is a member of the SRC family of cytoplasmic tyrosine kinases
(SFKs), involved in diverse inflammatory responses.
PDB 1Q33 (Crystal Structure of Human ADP-ribose pyrophosphatase NUDT9):
The human ADP-ribose pyrophosphatase NUDT9 belongs to a superfamily of Nudix hydrolases
that degrade potentially toxic compounds in the cell. The enzyme hydrolyzes ADP-ribose (ADPR)
to AMP and ribose 5'-phosphate. NUDT9 has 39% sequence similarity with the C-terminal