Journal of Applied Bioinformatics & Computational BiologyISSN: 2329-9533

Reach Us +1 850 754 6199

Research Article, J Appl Bioinforma Comput Biol Vol: 7 Issue: 2

Use of Chemo-Informatics to Identify Molecular Descriptors of Auxins, Cytokinins and Gibberellins

Ivan Andújar1, Daviel Gomez2, Lianny Perez3 and Jose Carlos Lorenzo2*

1Laboratory for Plant Cell and Tissue Culture, Bioplant Center, University of Ciego de Avila, Ciego de Avila, 69450, Cuba

2Laboratory for Plant Breeding & Conservation of Genetic Resources, Bioplant Center, University of Ciego de Avila, Ciego de Avila, 69450, Cuba

3 Laboratory for Metabolic Engineering, Bioplant Center, University of Ciego de Avila, Ciego de Avila, 69450, Cuba

*Corresponding Author : Jose Carlos Lorenzo
Laboratory for Plant Breeding & Conservation of Genetic Resources, Bioplant Center, University of Ciego de Avila, Ciego de Avila, 69450, Cuba
E-mail: [email protected]

Received: May 05, 2018 Accepted: May 25, 2018 Published: June 01, 2018

Citation: Andújar I, Gomez D, Perez L, Lorenzo JC (2018) Use of Chemo-Informatics to Identify Molecular Descriptors of Auxins, Cytokinins and Gibberellins. J Appl Bioinforma Comput Biol 7:2. doi: 10.4172/2329-9533.1000151

Abstract

We have identified those molecular descriptors differentiating four auxins, four cytokinins and four gibberellins. DRAGON software (version 5.5, 2007) and CambridgeSoft ChemOffice (version 12, 2010) including ChemDraw and Chem3D were used to calculate 212 molecular descriptors. Only 49 descriptors showed statistically significant differences among auxins, cytokinins and gibberellins. Of them, the most important differences can be described as follows. Gibberellins contain terminal tertiary C (sp3), terminal quaternary C (sp3), ring secondary C (sp3), ring tertiary C (sp3), and ring quaternary C (sp3) that are not present either in cytokinins or auxins. Gibberellins are also relatively rich in terminal secondary C (sp3) and 10-membered rings which are absent in cytokinins. Cytokinins have 10 times more nitrogen atoms than auxins but this atom is not present in gibberellins. Auxins have 10 times more substituted benzene C (sp2) and 5 times more benzene-like rings than cytokinins but these structures are not in gibberellins. Regarding the numbers of unsubstituted benzene C (sp2), auxins average 4.50, cytokinins 1.25 but they are absent in gibberellins. A dendogram was generated using data of those molecular descriptors with statistical significant differences (49). The three groups of regulators were correctly classified in three independent branches. The procedure described here may help identify new chemical compounds with potential uses as plant growth regulators.

Keywords: Chemo-informatics; Plant growth regulators; Molecular descriptors

Introduction

Auxins, cytokinins and gibberellins are by far the most important substances for regulating growth and morphogenesis in plant cell, tissue and organ culture [1-3]. Recently, for instance, in vitro rooting was enhanced in Nicotiana benthamiana by auxin indoleacetic acid [4]. Indolebutyric acid was recommended for shoot and root organogenesis of Eriocephalus africanus, a medicinal and aromatic plant species [5]. Naphthalene acetic acid significantly increased the number of bulblets developed on leaf explants of Scadoxus puniceus [6]. Callus cultures from leaves and young shoots of Taxus globosa were produced with 2,4-dichlorophenoxiacetic acid [7].

Examples of cytokinin use in plant in vitro culture can be found in the following papers. Date palm Phoenix dactylifera L. acclimatization was improved with the use of kinetin [8]. Micropropagation by axillary budding of Quercus ilex was achieved by culturing shoots with zeatin [9]. A reliable protocol was established for in vitro propagation of Artemisia nilagirica with N6-isopenteyladenine [10]. Heuchera villosa petioles were cultured with N6-benzyladenine to induce callus formation [11]. Regarding gibberellins, they have been used to control in vitro morphogenesis of potato [12], bromeliads [13] and peony [14].

In spite of the physiological effects of auxins, cytokinins and gibberellins have been frequently studied, their chemical dissimilarities to justify their differential impact on plants require more attention. The present study compared the molecular descriptors of indolebutyric acid, indoleacetic acid, 2,4-dichlorophenoxyacetic acid, 1-naphthaleneacetic acid (auxins), kinetin, zeatin, N6-isopentenyl adenine, N6-benzyladenine (cytokinins), GA1, GA3, GA4 and GA7 (gibberellins) (Figure 1).

Figure 1: Auxins, cytokinins and gibberellins compared.

Materials and Methods

DRAGON software (version 5.5, 2007) and Cambridge Soft Chem Office (version 12, 2010) including ChemDraw and Chem3D were used to calculate 212 molecular descriptors. All data of this study were statistically evaluated using SPSS (Version 8.0 for Windows, SPSS Inc., New York, NY) to perform One - Way ANOVA and Tukey (p=0.05). The overall coefficients of variation (OCV) were calculated as follows: (standard deviation/average) *100. In this formula, we considered the average values of the three growth regulators compared (auxins, cytokinins, gibberellins) to calculate the standard deviation and average. Therefore, the higher the difference between the three groups of chemicals, the higher is the OCV [15]. A hierarchical cluster analysis using the molecular descriptors for auxins, cytokinins and gibberellins was performed. The dendogram was built using average linkage (between groups). Variables were standardized to vary from 0 to 1 according to Kantardzic [16].

Results and Discussion

Even though 49 (out of 212) molecular descriptors showed statistically significant differences among auxins, cytokinins and gibberellins, based on the OCVs in (Table 1), only the numbers of terminal tertiary C (sp3), terminal quaternary C (sp3), ring secondary C (sp3), ring tertiary C (sp3), ring quaternary C (sp3), nitrogen atoms, substituted benzene C (sp2), benzene-like rings, terminal secondary C (sp3), 10-membered rings, and unsubstituted benzene C (sp2) were classified as ¨High¨ OCVs (116.94-173.21%). They indicated a remarkable distinction among these three groups of regulators.

  Auxins Cytokinins Gibberellins Auxins1 Cytokinins2 Gibberellins3 OCV4   Classification of OCV5
IBA IAA 2,4-D NAA KIN ZEA 2IP BA GA1 GA3 GA4 GA7
Number of terminal tertiary C (sp3) 0 0 0 0 0 0 0 0 5 6 5 5 0.00 ± 0.00b 0.00 ± 0.00b 5.25 ± 0.25a 173.21 High
Number of terminal quaternary C (sp3) 0 0 0 0 0 0 0 0 2 1 2 2 0.00 ± 0.00b 0.00 ± 0.00b 1.75 ± 0.25a 173.21 High
Number of ring secondary C (sp3) 0 0 0 0 0 0 0 0 5 5 7 5 0.00 ± 0.00b 0.00 ± 0.00b 5.50 ± 0.50a 173.21 High
Number of ring tertiary C (sp3) 0 0 0 0 0 0 0 0 5 6 5 5 0.00 ± 0.00b 0.00 ± 0.00b 5.25 ± 0.25a 173.21 High
Number of ring quaternary C (sp3) 0 0 0 0 0 0 0 0 2 1 2 2 0.00 ± 0.00b 0.00 ± 0.00b 1.75 ± 0.25a 173.21 High
Number of nitrogen atoms 1 1 0 0 5 5 5 5 0 0 0 0 0.50 ± 0.29b 5.00 ± 0.00a 0.00 ± 0.00b 150.21 High
Number of substituted benzene C (sp2) 2 2 3 3 0 0 0 1 0 0 0 0 2.50 ± 0.29a 0.25 ± 0.25b 0.00 ± 0.00b 150.21 High
Number of benzene-like rings 1 1 1 2 0 0 0 1 0 0 0 0 1.25 ± 0.25a 0.25 ± 0.25b 0.00 ± 0.00b 132.29 High
Number of terminal secondary C (sp3) 3 1 0 1 0 0 0 0 5 5 7 5 1.25 ± 0.63b 0.00 ± 0.00b 5.50 ± 0.50a 128.14 High
Number of 10-membered rings 0 0 0 1 0 0 0 0 1 1 1 1 0.25 ± 0.25b 0.00 ± 0.00b 1.00 ± 0.00a 124.9 High
Number of unsubstituted benzene C (sp2) 4 4 3 7 0 0 0 5 0 0 0 0 4.50 ± 0.87a 1.25 ± 1.25ab 0.00 ± 0.00b 121.19 High
Number of aliphatic secondary C (sp2) 0 0 0 0 0 1 1 0 2 2 0 2 0.00 ± 0.00b 0.50 ± 0.29ab 1.50 ± 0.50a 114.56 Medium
Number of double bonds 1 1 1 1 0 1 1 0 4 4 3 4 1.00 ± 0.00b 0.50 ± 0.29b 3.75 ± 0.25a 100 Medium
Number of aliphatic tertiary C (sp2) 0 0 0 0 0 1 1 0 1 1 1 1 0.00 ± 0.00b 0.50 ± 0.29ab 1.00 ± 0.00a 100 Medium
Number of circuits 3 3 1 3 4 3 3 4 15 15 15 15 2.50 ± 0.50b 3.50 ± 0.29b 15.00 ± 0.00a 99.23 Medium
Number of oxygen atoms 2 2 3 2 1 1 0 0 6 6 5 5 2.25 ± 0.25b 0.50 ± 0.29c 5.50 ± 0.29a 92.26 Medium
Number of hydroxyl groups 1 1 1 1 0 1 0 0 3 3 2 2 1.00 ± 0.00b 0.25 ± 0.25b 2.50 ± 0.29a 91.65 Medium
Number of aromatic bonds 10 10 6 11 15 10 10 16 0 0 0 0 9.25 ± 1.11a 12.75 ± 1.60a 0.00 ± 0.00b 89.83 Medium
Aromatic ratio 0.625 0.714 0.462 0.73 0.833 0.588 0.625 0.842 0 0 0 0 0.63 ± 0.06a 0.72 ± 0.07a 0.00 ± 0.00b 87.16 Medium
Number of aromatic C (sp2) 8 8 6 10 9 5 5 11 0 0 0 0 8.00 ± 0.82a 7.50 ± 1.50a 0.00 ± 0.00b 86.74 Medium
Squared Ghose-Crippen octanol-water partition coefficient. (log^P) 7.156 3.107 7.907 5.653 1.186 0.235 2.483 2.869 0.174 0 2.8 2.246 5.96 ± 1.06a 1.69 ± 0.60b 1.31 ± 0.71b 86.45 Medium
Number of 5-membered rings 1 1 0 0 2 1 1 1 3 3 3 3 0.50 ± 0.29b 1.25 ± 0.25b 3.00 ± 0.00a 81.03 Medium
Rotatable bond fraction 0.138 0.087 0.158 0.08 0.111 0.133 0.103 0.1 0.02 0.021 0.019 0.02 0.12 ± 0.02a 0.11 ± 0.01a 0.02 ± 0.00b 65.65 Medium
Number of 9-membered rings 1 1 0 0 1 1 1 1 2 2 2 2 0.50 ± 0.29b 1.00 ± 0.00b 2.00 ± 0.00a 65.47 Medium
Number of rings 2 2 1 2 3 2 2 3 5 5 5 5 1.75 ± 0.25b 2.50 ± 0.29b 5.00 ± 0.00a 55.19 Low
Number of multiple bonds 11 11 7 12 15 11 11 16 4 4 3 4 10.25 ± 1.11a 13.25 ± 1.31a 3.75 ± 0.25b 53.46 Low
Ghose-Crippen octanol-water partition coefficient (logP) 2.675 1.763 2.812 2.378 1.089 0.485 1.576 1.694 0.417 0.001 1.673 1.499 2.41 ± 0.23a 1.21 ± 0.28ab 0.90 ± 0.41b 52.92 Low
Number of rotatable bonds 4 2 3 2 3 4 3 3 1 1 1 1 2.75 ± 0.48a 3.25 ± 0.25a 1.00 ± 0.00b 50.63 Low
Number of hydrogen atoms 13 9 6 10 9 13 13 11 22 20 24 22 9.50 ± 1.44b 11.50 ± 0.96b 22.00 ± 0.82a 46.84 Low
Number of acceptor atoms for H-bonds (N.O.F) 2 2 3 2 5 5 4 4 6 6 5 5 2.25 ± 0.25b 4.50 ± 0.29a 5.50 ± 0.29a 40.77 Low
Number of bonds 29 23 19 25 27 30 29 30 51 48 52 50 24.00 ± 2.08b 29.00 ± 0.71b 50.25 ± 0.85a 40.5 Low
Number of atoms 28 22 19 24 25 29 28 28 47 44 48 46 23.25 ± 1.89b 27.50 ± 0.87b 46.25 ± 0.85a 37.85 Low
Sum of atomic Sanderson Electronegativities (scaled on Carbon atom) 28.06 22.29 20.16 24.07 25.6 29.37 28.04 28.16 47.68 44.8 48.24 46.36 23.65 ± 1.67b 27.79 ± 0.79b 46.77 ± 0.77a 37.66 Low
Number of non-H bonds 16 14 13 15 18 17 16 19 29 28 28 28 14.50 ± 0.65c 17.50 ± 0.65b 28.25 ± 0.25a 36 Low
Number of carbon atoms 12 10 8 12 10 10 10 12 19 18 19 19 10.50 ± 0.96b 10.50 ± 0.50b 18.75 ± 0.25a 35.95 Low
Sum of Kier-Hall electrotopological states 36.67 33.67 38.89 35.17 35.67 37.67 32.17 36.17 65.83 63.92 58.92 59.92 36.10 ± 1.11b 35.4 ± 1.16b 62.15 ± 1.64a 34.2 Low
Sum of atomic polarizabilities (scaled on carbon atom) 18.48 14.96 14.12 16.72 17.01 18.53 18.07 19.31 30.1 28.34 30.41 29.65 16.07 ± 0.97b 18.23 ± 0.48b 29.63 ± 0.46a 34.18 Low
Sum of atomic Van der Waals volumes (scaled on carbon atom) 17.6 14.41 13.33 16.01 16.68 17.87 17.36 18.76 28.65 27.05 28.73 28.13 15.34 ± 0.93a 17.67 ± 0.44b 28.14 ± 0.39b 33.46 Low
Topological polar surface area using N.O polar contributions 53.09 53.09 46.53 37.3 79.63 86.72 66.49 66.49 104.06 104.06 83.83 83.83 47.50 ± 3.74b 74.83 ± 5.03a 93.95 ± 5.84a 32.38 Low
Topological polar surface area using N.O.S.P polar contributions 53.09 53.09 46.53 37.3 79.63 86.72 66.49 66.49 104.06 104.06 83.83 83.83 47.50 ± 3.74b 74.83 ± 5.03a 93.95 ± 5.84a 32.38 Low
Numb of non-N atom 15 13 13 14 16 16 15 17 25 24 24 24 13.75 ± 0.48c 16.00 ± 0.41b 24.25 ± 0.25a 30.71 Low
Molecular weight 203.26 175.2 221.04 186.22 215.24 219.28 203.28 225.28 346.41 332.38 332.43 330.41 196.43 ± 10.03b 215.77 ± 4.65b 335.41 ± 3.70a 30.21 Low
Number of 6-membered rings 1 1 1 2 1 1 1 2 2 2 2 2 1.25 ± 0.25b 1.25 ± 0.25b 2.00 ± 0.00a 28.87 Low
Unsaturation index 3.585 3.585 3 3.7 4 3.585 3.585 4.087 2.322 2.322 2 2.322 3.47 ± 0.16a 3.81 ± 0.13a 2.24 ± 0.08b 26.03 Low
Ghose-Crippen molar refractivity 57.654 48.452 48.366 53.816 57.686 61.575 59.8 65.295 86.414 81.913 84.078 84.887 52.07 ± 2.26c 61.09 ± 1.61b 84.32 ± 0.94a 25.28 Low
Sum of conventional bond orders (H-depleted) 22 20 17 21.5 25.5 23 22 27 33 32 31 32 20.13 ± 1.13c 24.38 ± 1.14b 32.00 ± 0.41a 23.6 Low
Mean electrotopological state 2.44 2.59 2.99 2.51 2.23 2.35 2.14 2.13 2.63 2.66 2.45 2.5 2.63 ± 0.12a 2.21 ± 0.05b 2.56 ± 0.05a 9.1 Low
Mean atomic van der Waals volume (scaled on carbon atom) 0.63 0.65 0.7 0.67 0.67 0.62 0.62 0.67 0.61 0.61 0.6 0.61 0.66 ± 0.01a 0.65 ± 0.01a 0.61 ± 0.00b 4.4 Low
Mean atomic polarizability (scaled on carbon atom) 0.66 0.68 0.74 0.7 0.68 0.64 0.62 0.69 0.64 0.64 0.63 0.64 0.70 ± 0.02a 0.60 ± 0.02ab 0.64 ± 0.00b 4.4 Low

Table 1: Comparison of molecular descriptors for auxins. cytokinins and gibberellins. IBA: Indolebutyric acid; IAA: Indoleacetic acid; 2,4-D: 2,4-dichlorophenoxyacetic acid; NAA: 1-Naphthaleneacetic acid; KIN: Kinetin; ZEA: Zeatin; 2IP: N6 – isopentenyladenine; BA: N6-benzyladenine; GA1: Gibberellin 1; GA3: Gibberellin 3; GA4: Gibberellin 4; GA7: Gibberellin 7.

Gibberellins contain terminal tertiary C (sp3), terminal quaternary C (sp3), ring secondary C (sp3), ring tertiary C (sp3), and ring quaternary C (sp3) that are not present either in cytokinins or auxins. Gibberellins are also relatively rich in terminal secondary C (sp3) (4.4 times more than auxins =5.50/1.25) and 10-membered rings (4 times more than auxins=1.00/0.25) which are absent in cytokinins.

Cytokinins have 10 times more nitrogen atoms than auxins (5.00/0.50) but this atom is not present in gibberellins. Auxins have 10 times more substituted benzene C (sp2) and 5 times more benzene-like rings than cytokinins (2.50/0.25 and 1.25/0.25, respectively) but these structures are not in gibberellins. Regarding the numbers of unsubstituted benzene C (sp2), auxins average 4.50, cytokinins 1.25 but they are absent in gibberellins.

¨Medium¨ OCVs (60.67 to 116.94%) remarkably distinguished gibberellins from auxins and cytokinins (Table 1). Gibberellins have 3 times more aliphatic secondary C (sp2) and 2 times more aliphatic tertiary C (sp2) than cytokinins (1.50/0.50; 1.00/0.50; respectively) but these types of atoms are not in auxins. Gibberellins are also rich in double bonds (7.5 times more than cytokinins=3.75 /0.50 and 3.75 times more than auxins=3.75/1.00), circuits (4.3 times more than cytokinins=15.0/3.5 and 6 times more than auxins=15.0/2.5), and oxygen atoms (11 times more than cytokinins=5.50/0.50 and 2.4 times more than auxins=5.50/2.25).

The numbers of hydroxyl groups, 5-membered and 9-membered rings are also higher in gibberellins: 10 times more hydroxyl groups than cytokinins (2.50/0.25) and 2.5 times more than auxins (2.50/1.00); 2.4 times more 5-membered rings than cytokinins (3.00/1.25) and 6 times more than auxins (3.00/0.50); and 2 times more 9-membered rings than cytokinins (2.00/1.00) and 4 times more than auxins (2.00/0.50). Contrastingly, gibberellins do not have either aromatic bonds (cytokinins: 12.75; auxins: 9.25) or aromatic C (sp2) (cytokinins: 7.50; auxins: 8.00). Aromatic ratio is cero in gibberellins while 0.72 in cytokinins and 0.63 in auxins. On the other hand, the rotatable bond fraction is lower in gibberellins (0.02) compared to auxins (0.12) or cytokinins (0.11). It is important to note the squared Ghose-Crippen octanol-water partition coefficient is remarkably higher in auxins (5.96) in comparison with cytokinins (1.69) and gibberellins (1.31).

Descriptors shown in Table 1 were used to generate the dendogram shown in Figure 2 which correctly classified the three groups of regulators in three independent branches. Molecular descriptors have been applied to describe biological activities, in many studies showing their applicability as an attractive tool for efficient (e.g.) drug design process [17-19].

Figure 2: Hierarchical cluster analysis using the molecular descriptors for auxins, cytokinins and gibberellins. Only those descriptors with statistical significant differences among auxins, cytokinins and gibberellins were included (Table 1). The dendogram was built using average linkage (between groups). Variables were standardized to vary from 0 to 1 according to Kantardzic [16].

To end we would like to emphasize the effectiveness of the chemoinformatics procedure described here to differentiate auxins, cytokinins and gibberellins and also in the search for new plant growth regulators with potential applications in modern in vitro culture and agriculture. Molecular descriptors of new chemical compounds can be determined and included in the dendogram shown in Figure 2. If new chemicals are located, for instance, near auxins they can be regarded as potential auxinlike compounds, although this should be later tested experimentally.

Author Contribution

I.A., D.G., L.P. and J.C.L. designed the research, analyzed the data and wrote the paper. J.C.L. had primary responsibility for the final content. All authors have read and approved the final manuscript.

Acknowledgements

This research was supported by the Bioplant Centre (University of Ciego de Ávila, Cuba).

References

Track Your Manuscript

Recommended Conferences

Share This Page