Interdiscip Sci Comput Life Sci (2013) 5: 280–285

DOI: 10.1007/s12539-013-0152-2

Studies on Interaction of Insect Repellent Compounds with Odorant

Binding Receptor Proteins by in silico Molecular Docking Approach

J. Vinay GOPAL, K. KANNABIRAN∗

(Division of Biomolecules and Genetics, School of Biosciences and Technology, VIT University, Vellore 632014, India)

Received 14 August 2012 / Revised 27 November 2012 / Accepted 21 January 2013

Abstract: The aim of the study was to identify the interactions between insect repellent compounds and tar-
get olfactory proteins. Four compounds, camphor (C10 H16 O), carvacrol (C10 H14 O), oleic acid (C18 H34 O2 ) and
firmotox (C22 H28 O5 ) were chosen as ligands. Seven olfactory proteins of insects with PDB IDs: 3K1E, 1QWV,
1TUJ, 1OOF, 2ERB, 3R1O and OBP1 were chosen for docking analysis. Patch dock was used and pymol for
visualizing the structures. The interactions of these ligands with few odorant binding proteins showed binding
energies. The ligand camphor had showed a binding energy of −136 kcal/mol with OBP1 protein. The ligand
carvacrol interacted with 1QWV and 1TUJ proteins with a least binding energy of −117.45 kcal/mol and −21.78
kcal/mol respectively. The ligand oleic acid interacted with 1OOF, 2ERB, 3R1O and OBP1 with least binding
energies. Ligand firmotox interacted with OBP1 and showed least binding energies. Three ligands (camphor,
oleic acid and firmotox) had one, two, three interactions with a single protein OBP1 of Nilaparvatha lugens (Rice
pest). From this in silico study we identified the interaction patterns for insect repellent compounds with the
target insect odarant proteins. The results of our study revealed that the chosen ligands showed hydrogen bond
interactions with the target olfactory receptor proteins.
Key words: patch dock, pymol, insect repellent compounds, odarant binding proteins.

1 Introduction In silico and computational simulation methods are

Repellents are substances that deter insects from
biting and landing on human or animal skin surface
(Blackwell et al., 2003). The use of synthetic repellents
has increased worldwide especially to prevent spoilage
of fruits, grains and to control vector-borne diseases like
malaria, dengue and yellow fever (Nerio et al., 2009).
Synthetic repellents used to control insects may have
severe effects on environment and human health (Pita-
sawat et al., 2003). Thus there is a tendency to increase
the usage of natural and environment friendly repellents
due to their low toxicity and safety (Katz et al., 2008).
In the last 50 years many plants have been screened
for novel repellents and insecticide activities (Sukumar
et al., 1991). The major proteins of the insect olfac-
tory system are the odarant binding proteins (OBPs)
(Vogt et al., 1981). Insect OBPs are of three types,
pheromone binding proteins (PBPs), general odarant
binding proteins and antennal binding proteins (AB-
PXs) (Zhou et al., 2010). These OBPs are small soluble
proteins that help in transport of signals from odarant
compounds to brain that mediate insect behavioural
response (Xu et al., 2010).
∗ A total of 7 proteins were selected as targets for dock-
Corresponding author.
E-mail: kkb@vit.ac.in
useful for making logistic predictions and hypothesizing
to find out solutions in the areas of medicine and drug
formulation. The use of natural products with insect
repellent property can be identified by using in silico
molecular docking tools. These methods provide suit-
able insights into identifying binding residues responsi-
ble for a biological function. In this study we performed
docking of certain natural repellent compounds with ol-
factory proteins of insects to understand their binding
patterns.
2 Materials and methods
2.1 Ligands
The ligand molecules selected for this study were
camphor (C10 H16 O), carvacrol (C10 H14 O), oleic acid
(C18 H34 O2 ) and firmotox (C22 H28 O5 ). The 3D confor-
mations of the compounds were obtained from NCBI
database by copying the canonical smiles in CORINA
software (Fig. 1).
.
2.2 Target proteins
ing which include odorant binding proteins with PDB
Interdiscip Sci Comput Life Sci (2013) 5: 280–285 281

OH

O
(a) (b)
OH
O

O
O O
O
O

(c) (d)
Fig. 1 Chemical structures. (a) Camphor; (b) Carvacrol; (c) Oleic acid; (d) Firmotox.

IDs: 3K1E, 1QWV, 1TUJ, 1OOF, 2ERB, 3R1O and
a modelled protein OBP1 of Nilaparvatha lugens us-
ing i-Tasser (http://zhanglab.ccmb.med.umich.edu/I-
TASSER/).
2.3 Molecular docking studies
Molecular docking was carried out using patch dock
online tool. The input file was in the form of PDB code
of the receptor or pdb file format and the molecules
were in pdb file format. The output file was as a docking
report. The docked image was viewed by “Pymol 1.3”
software. The interactions between ligands and pro-
teins were also seen with the length of the interaction
along with amino acids involved in these interactions
and it was calculated by using “Pymol 1.3” software.
The binding energy was calculated by Atomic contact
energy (ACE) according to Zhang et al. (1997).
3 Results and discussion
The four different natural repellent compounds were
docked with seven odarant receptor proteins (Fig. 2).

C10H16O 3K1E OBP1

C10H14O 1QWV 1TUJ

C18H34O2 1OOF 2ERB 3R1O OBP1

C22H28O5 OBP1
Fig. 2 In silico molecular docking analysis of four target compounds against seven odarant binding proteins (OBPs).
282 Interdiscip Sci Comput Life Sci (2013) 5: 280–285

Out of the four ligands the first compound camphor
(IUPAC name: 4, 7, 7-trimethylbicyclo [2.2.1] heptan-
3-one), possesses 16 non polar hydrogens. The dock-
ing of camphor with seven odorant binding proteins
resulted with two interactions between the ligand and
receptor proteins 3K1E and OBP1. Camphor showed
aminoacid interactions with 3K1E protein from Aedes
aegyptii with a least binding energy of −4.14 kcal/mol
and OBP1 modelled protein of Nilaparvatha lugens (rice
pest pathogen) with a least binding energy of −136.34
kcal/mol. One interaction was observed between cam-
phor and 3K1E protein (Table 1).

Table 1 Docking results of insect repellent compounds against olfactory receptor proteins

Ligand Target proteins Score Area ACE (kcal/M) Hydrogen bond

Camphor 3K1E (Aedes aegypti) 2290 234.30 −4.14 1

(C10 H16 O) OBP1 (Nilaparvatha lugens) 3218 359 −136.34 1

Carvacrol 1QWV (Antheraea Polyphemus) 3214 342 −117.45 1

(C10 H14 O) 1TUJ (Apis mellifera) 3272 375 −21.78 1

Oleic acid 1OOF (Drosophila melanogaster) 4924 593 −245.17 1

(C18 H34 O2 ) 2ERB (Anopheles gambiae) 4376 489 −82.75 1
3R1O (Anopheles gambiae) 4572 548 −18.24 1
OBP1 (Nilaparvatha lugens) 4954 589 −42.89 2

Firmotox OBP1 (Nilaparvatha lugens) 5172 684 −70.15 3

(C22 H28 O5 )

The length of the interaction between the ligand and

the target protein was 3.0 Å. Lysine is situated at 112th
PHE-169
position in the amino acid sequence of 3K1E protein
and it has 9 atoms (Fig. 3).
3.3

3.0
LYS-112

Fig. 4 In silico binding of camphor with OBP1 from Nila-

parvatha lugens.

methyl-5-propan-2-ylphenol), has 13 non polar hydro-

Fig. 3 In silico binding of camphor with 3K1E protein.
A single interaction was observed between amino acid
phenylalanine and camphor (ligand). The length of the
interaction was calculated as 3.3 Å. Phenylalanine was
located at 169th position in the amino acid sequence of
i TASSER modelled protein OBP1 from Nilaparvatha
lugens and it has 11 atoms (Fig. 4).
The second compound carvacrol (IUPAC name: 2-
gens, 6 aromatic carbons and 2 rotatable bonds. The
ligand showed interactions with pheromone binding
protein (PDB ID: 1QWV from Antheraea polyphemus)
and odorant binding protein (1TUJ from Apis mellif-
era) with least binding energies of −117.45 and −21.78
kcal/mol respectively. Isoleucine at 52nd position had
interaction with 1QWV protein with bond length of 2.0
Å and contains 19 atoms (Fig. 5). Carvacrol interacted
with serine at 123rd position of 1TUJ, an odorant bind-
Interdiscip Sci Comput Life Sci (2013) 5: 280–285
ILE-52 2.0
Fig. 5 In silico binding of carvacrol with 1QWV protein.
SER-123
1.5
Fig. 6 In silico binding of carvacrol with 1TUJ protein.
ing protein from Apis mellifera with a bond length of
1.5 Å and has 11 atoms (Fig. 6).
The third compound oleic acid (IUPAC name: (Z)-
octadec-9-enoic acid), has 33 non polar hydrogens and
16 rotatable bonds. This ligand interacted with four
proteins 1OOF, 2ERB, 3R1O and OBP1 from Nila-
parvatha lugens. The ligand interacted with glutamine
residue (5th position) from Drosophila melanogaster
with nine atoms and a binding energy of −245.47
kcal/mol and the length of interaction was 3.4 Å
(Fig. 7).
Oleic acid showed interaction with aspartic acid (at
67th position) of 2ERB protein from Anopheles gambiae
with a binding energy of −82.75 kcal/mol and bond
283
GLN-5 3.4
Fig. 7 In silico binding of oleic acid with 1OOF protein.
SF
S 2
F-67 2.9
Fig. 8 In silico binding of oleic acid with 2ERB protein.
length of 2.9 Å, and it possesses 8 atoms (Fig. 8).
The oleic acid interacted with odarant protein from
Anopheles gambiae and two interactions with OBP1
protein from Nilaparvatha lugens also occurred. Ty-
rosine at 74th position showed binding with 3R1O pro-
tein with 24 atoms and bond length of 2.8 Å (Fig. 9).
The ligand also interacted with OBP1 protein with glu-
tamine and lysine residues at 61st and 64th positions
with a bond length of 2.1 Å and 2.9 Å respectively
(Fig. 10).
Firmotox (IUPAC Name: [2-methyl-4-oxo-3-[(2Z)-
penta-2, 4-dienyl] cyclopent-2-en-1-yl](1R, 3R)-3-[(E)-
2-acetyloxyprop-1-enyl]-2, 2dimethylcyclo propane-1-
carboxylate), has 28 non-polar hydrogens, 8 aromatic
carbons and 9 rotatable bonds. The ligand interacted
with OBP1 protein from Nilaparvatha lugens. The
284
TYR-74
2.8
Fig. 9 In silico binding of oleic acid with 3R1O.
GLU-61
2.1
2.9
LYS-64
Fig. 10 In silico binding of oleic acid with OBP1 from Ni-
laparvatha lugens.
amino acids involved were lysine at 64th position with
9 atoms, 75th position containing 9 atoms and serine at
71st position with 6 atoms. The bond lengths for lysine
at 64th and 75th positions were 3.0 Å and 1.8 Å respec-
tively, and the bond length of serine at 71st position
was 3.4 Å (Fig. 11).
Structure based modelling predictions may facilitate
the design of novel repellents with increased binding
affinity and selectivity (Tsitsanou et al., 2012). Some
monoterpenes such as camphor and carvacrol are con-
stituents of essential oils and were reported to have
mosquito repellent activity (Ibrahim et al., 1998; Jaen-
son et al., 2006; Park et al., 2005; Yang et al., 2004).
Insect odarant binding proteins are components of ol-
factory system that binds to attractant and repellent
Interdiscip Sci Comput Life Sci (2013) 5: 280–285
LYS-64
3.0
3.4
1.8
Fig. 11 In silico binding of firmotox with OBP1 from Ni-
laparvatha lugens.
odours, OBP1 protein was reported to show high bind-
ing affinity to camphor and some structurally related
compounds.
4 Conclusions
We concluded that the hydrogen bond interactions
occurred involving the amino acid residues of the target
odarant receptor proteins (PDB IDs: 3K1E, 1QWV,
1TUJ, 2ERB, 1OOF, 3R1O and OBP1) of Nilaparvath
a with selected ligands (camphor, carvacrol, oleic acid
and firmotox) which are often used for insecticidal re-
pellent activity. These results further substantiate the
use of in silico tools for identifying novel insect repellent
compounds.
Acknowledgements
Authors thank the management of VIT University for
providing necessary facilities to carry out this study.
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