Study on interactions of nanocurcumin with dna molecules

VIETNAM NATIONAL UNIVERSITY, HANOI VIETNAM JAPAN UNIVERSITY - NGUYEN THI TUOI STUDY ON INTERACTIONS OF NANOCURCUMIN WITH DNA MOLECULES MASTER'S THESIS Hanoi, 2018 VIETNAM NATIONAL UNIVERSITY, HANOI VIETNAM JAPAN UNIVERSITY NGUYEN THI TUOI STUDY ON INTERACTIONS OF NANOCURCUMIN WITH DNA MOLECULES MAJOR: NANOTECHNOLOGY SUPERVISORS: Associate Prof Dr NONG VAN HAI Hanoi, 2018 Acknowledgement First and foremost, I want to express my heartfelt-thanks to my supervisor Assoc Prof Dr Nong Van Hai, Institute of Genome Research, Vietnam Academy of Science and Technology and my supervisor during my internship in Japan Prof Dr Kei Yura, Ochanomizu University They have offered me invaluable support and precious instructions during my time as a master student in Vietnam Japan University Without their infinite patience and encouragement, this thesis would never be completed successfully I express my sincere admiration to Assoc Prof Dr Pham Huu Ly, Institute of Chemistry, Vietnam Academy of Science and Technology for generous gift of Curcumin substance Thirdly, I would like to show my sincerest appreciation to all members of Institute of Genome Research, Vietnam Academy of Science and Technology for their valuable guidance and assistance, which helped me to gain much knowledge I want to send my thanks to the professors and the staff members of Vietnam Japan University, Vietnam National University, who have taught me with new knowledge and assisted me during my study Finally, to all those who have aided me in doing this thesis but were not mentioned here, I am truly grateful for your help June 2018 Nguyen Thi Tuoi LIST OF CONTENTS INTRODUCTION CHAPTER LITERATURE REVIEW 1.1 Overview of Curcumin 1.2 Overview of DNA CHAPTER MATERIALS AND EXPERIMENTTAL METHOD 2.1 Computational researches 2.1.1 Purpose of computational research 2.1.2 Input data 2.1.3 Method and processing 2.2 The empirical research 14 2.2.1 Purpose of empirical research 14 2.2.2 Subjects of research 14 2.2.3 Equipment 14 2.2.3 Experimental methods 14 CHAPTER RESULTS AND DISCUSSION 18 3.1 Computational research results 18 3.1.1 Virtual screening and molecular docking 18 3.1.2 Molecular dynamics simulation 20 3.2 Results of empirical research results 25 3.2.1 DNA amplification 25 3.2.2 FTIR results 26 CONCLUSION 29 LIST OF TABLES Table 2.1 The MD algorithm Table 2.2 Equipment used in empirical study Table 2.3 PCR mixture for 10 µl reaction Table 2.4 Primer sequences Table 2.5 Absorption peaks of algal polysaccharides on FTIR spectra [5] Table 3.1 Docking scores of compounds for Enol and Keto forms of Curcumin Table 3.2 Hydrogen bonds from docking results 10 14 15 16 17 18 19 LIST OF FIGURES Figure 1.1 Curcuma longa plant (A) and Curcuma longa rhizome (B) Figure 1.2 Keto (A) and Enol (B) forms of Curcumin … Figure 2.1 The 3-D structures of Curcumin’s Enol form (A), Keto form (B) and DNA (C) Figure 2.2 Process of computational research … Figure 2.3 Grid box for molecular docking Figure 2.4 Atom box for Gromacs simulation 13 Figure 2.5 Thermal cycle of a PCR reaction … 15 Figure 2.6 Schematic diagram of FTIR 17 Figure 3.1 Docking complexes for Curcumin’s Enol form (A) and Keto form (B) 18 Figure 3.2 Energy potential of Keto-DNA system 21 Figure 3.3 Energy potential of Enol-DNA system 21 Figure 3.4 Pressure of Keto-DNA system (A) and Enol-DNA system (B) 22 Figure 3.5 Temperature of Keto-DNA system (A) and Enol-DNA system (B) 22 Figure 3.6 RMSD evolution of Keto-DNA system (A) and Enol-DNA system 23 (B) 23 Figure 3.7 Density of Keto-DNA system (A) and Enol-DNA system (B) 23 Figure 3.8 Three of 101 conformations of DNA and Curcumin’s Keto form 24 Figure 3.9 Three of 101 conformations of DNA and Curcumin’s Enol form 24 Figure 3.10 Electrophoretic result of PCR products 26 Figure 3.11 FTIR image of DNA 26 Figure 3.12 FTIR image of Curcumin 27 Figure 3.13 FTIR image of DNA-Curcumin mixture 27 LIST OF ABBREVIATIONS Abbreviation Description CUR Curcumin MD Molecular Dynamics DNA Deoxyribonucleic Acid bp Base pair dNTP Deoxynucleotide Kb Kilobase RNA Ribonucleic Acid miRNA Micro RNA mRNA Messenger RNA PCR Polymerase Chain Reaction FTIR Fourier Transform Infrared INTRODUCTION In recent years, dietary supplements have become more popular in health care, with ingredients derived from food sources, which are considered as special food and safety history of use, however, their real impacts are still a problem to be addressed about the safety, the risks as well as the potential interactions with other substances Dietary supplements are defined as a healthy food, which can be circulated without encountering rigorous clinical tests as drugs (by the Dietary Supplement Health and Education Act, USA (DSHEA) in 1994), it means that the products are put into use until being proven to be unsafe Moreover, the "supposedly functional" substances in dietary supplements are usually synthesized with high concentrations and small molecules that can be easily penetrated into cells and exposed to molecules Therefore, while functional products are increasingly used, understanding their interactions with molecules in the body is essential for preventing possible risks In many Asia countries such as Vietnam, India, Thailand, China, Yellow Turmeric (Curcuma longa) is considered as a multipurpose medicinal plant Many dietary supplements, which contain a prominent key component – the so-called Curcumin extracted from yellow Turmeric, have been produced and widely used Due to its insolubility in water, to produce high levels of penetration into the cell, Curcumin is usually made in the form of nanometer-sized particles, commonly referred to as Nano Curcumin While the amount of Curcumin can penetrate into cells is significant (Curcumin nanoparticles typically prefer the size of 20-60 nm whereas transmembrane holes usually range from 100-200 nanometers), the specific activity has not been exactly identified Recent studies demonstrated that Curcumin has a wide range of pharmacological activities, such as anti-cancer agent, prooxidant properties and antioxidant factor, by the interaction with cellular molecules, including DNA, proteins and RNA, especially DNA However, the interaction between Curcumin and DNA has not been elucidated Therefore, in order to determine the impacts of Curcumin on macromolecular molecules in human cell, we have studied the interaction of Curcumin with the specific cellular DNA fragments This research has been carried out with two main objectives: - Computational study on the interaction between the Curcumin and the DNA molecules - Empirical study on the interaction between Curcumin nanoparticles and DNA by using Fourier Transform Infrared (FTIR) Spectroscopy method CHAPTER LITERATURE REVIEW 1.1 Overview of Curcumin Turmeric Turmeric (Curcuma longa) has long been popular used in cuisine as well as in oriental medicine especially in India, China, Thailand and Vietnam, having rhizome fleshy, much branched and yellow orange (Figure 1.1) It is a blossoming herbaceous plant of the ginger family (Zingiberacea), growing rapidly at 20-30oC and high humidity, so it is widely distributed throughout the South Asia Turmeric’s rhizome is one of the main ingredients in many countries, especially in India, which is a largest exporter and also used more than 80% of it Turmeric’s powder is used to create an orange-yellow color and smell characteristic for food According to traditional medicine, several pharmacological activities of Turmeric are known in many diseases: diabetes, edama, hemorrhoids, urinary disease, anemia, inflammation, liver disorders and skin disease To cure a lot of health disorder, Indians often use extracts from turmeric to treat skin disease, while Chinese medicine used for infected problems Turmeric contains Carbohydrates (60-70%), Moisture (6-13%), Protein (68%), Fat (5-10%) and Minerals (3-7%), Fiber (2-7%), Essential oils (3-7%) and Curcuminoids (1-6%) Curcuminoids are members of group including Curcumin and 12 Curcumin-like substances Curcumin is the most critical Curcuminoid substances, accounting for around 70% of all Curcuminoids (around 3% to 6% of turmeric’s rhizome) Except Curcumin, this class of compounds likewise incorporates demethoxycurcumin (10-20%), bisdemethoxy Curcumin (10%) and HexahydroCurcumin [18] A B Figure 1.1 Curcuma longa plant (A) and Curcuma longa rhizome (B) Curcumin Curcumin is a non-harmful natural substance, also known as Diferuloylmethane, Natural Yellow 3, Turmeric Yellow, extracted from turmeric and has been utilized for a considerable length of time as dietary supplement and remedial specialist in Chinese and Asian medications The UPAC name of Curcumin is 1,7-bis (4-hydroxy-3-methoxy phenyl)-1,6-heptadiene-3, 5-dione (1E6E) with molecular formula of C21H20O6, molecular weight: 368.385 g/mol and the melting point: 183 °C [26] On UV spectra, the absorption of Curcumin occurs around 400-430 nm, depending on solvent, in ethanol the maximum is at 426 nm Curcumin is insoluble in water and ether, soluble in alcohol and glacial acetic acid, very soluble in ethanol and acetic acid [11] About the color, Curcumin gives orange-yellow in the natural environment, brownish-red color in alkali medium, light-yellow color in acid medium [26] Chemically, two possible structures of Curcumin can exist: Keto tautomer form and Enol tautomer form (Figure 1.2) As such, Curcumin is stables in equilibrium with the Enol form The bis-keton form prevails in neutral aqueous and acidic solutions At pH 3-7, Curcumin goes about as a strong H-atom donor [24] Conversely, above pH 8, the Enol form predominates, and Curcumin has a role as an electron donor [21] A B Figure 1.2 Keto (A) and Enol (B) forms of Curcumin Curcumin and human diseases Curcumin has been widely reported to have anticancer and anti-inflammatory activities Although the exact mode of action of Curcumin on tumors remains elusive, many mechanisms have been proposed including the effect on apoptosis, affecting some enzymes features such as glutathione S-transferases, antioxidation and binding specifically to DNA, proteins and RNA - cellular structural molecules [25] Davis et al proved that Curcumin affected the expression of miRNA in human pancreatic cancer [3] Specifically, Curcumin had been shown to be an inhibitor of the synthesis of 99 mRNA and as an enhancer of miRNA-22 activity The increased activity of these miRNAs reduced the expression of estrogen receptor gene, thereby inhibiting the growth of pancreatic cancer cells Curcumin has been proved to inhibit the AP-1 activation by Huang et al [6] AP-1 is known as a substance that is Molecular dynamics simulation Energy potential After the systems were possible to perform the Gromacs simulation, the energy of systems need to be minimized to remove any local strain In energy minimization step of both the systems between two Curcumin’s forms and DNA molecule, the potential was drastically reduced in the first ps and remained around the average value (~ -323000 kJ/mol) Then, the potential was maintained at an average of about -367000 kJ/mol in the equilibration and production steps (Figure 3.2, 3.3) Temperature The temperature progressions are described in figure 3.4 The plots show that the temperature of two systems quickly reached the target value about 300K and remained stable during 1000 ps of equilibration and production steps Pressure The pressure values of two systems fluctuate widely from -400 bar to 400 bar over the course of the 1000-ps equilibration step In the Keto-DNA system, the average value of the pressure is about 0.032 bar With Enol-DNA system, the average value is approximately 0.378 bar (Figure 3.5) Density The density values over the course of 1000 ps are showed in figure 3.6 with the fluctuated range 995-1010 kg/m3 The average value of Keto system is about 1002.88 kg/m3, similar to the Enol system with 1002.79 kg/m3 of density average value RMSD evolution The 1000 ps trajectories of two systems were stable as indicated by the stabilization of the RMS deviation value The RMS deviation of the system including Curcumin’s Enol form stabilized at an average value of ~ 0.2 nm and that of Keto form was similar with the RMSD average value ~0.22 nm The Curcumin’s oscillation curves were relatively overlapping with the fluctuations of the DNACUR complexes in both the systems of two kind of Curcumin’s form (Figure 3.7) 20 Figure 3.2 Energy potential of Keto-DNA system Figure 3.3 Energy potential of Enol-DNA system 21 Figure 3.4 Temperature of Keto-DNA system (A) and EnolDNA system (B) Figure 3.5 Pressure of Keto-DNA system (A) and Enol-DNA system (B) 22 Figure 3.6 Density of Keto-DNA system (A) and EnolDNA system (B) Figure 3.7 RMSD evolution of DNA-Keto system (A) and DNA-Enol system (B) 23 Master Thesis | Nguyen Thi Tuoi Simulated conformations All the Gromacs simulations were default in 500000 steps and 1000 ps For each system, the simulation results gave 101 different conformations; some interaction conformations between Curcumin and DNA are shown in figure 3.8 for the Curcumin’s Keto form and figure 3.9 for the Enol form In the system of Keto form, unlike the docking results, the Curcumin molecule tended to leak out of the DNA minor groove in all simulated conformations A B C Figure 3.8 Three (A, B, C) of 101 conformations of DNA and Curcumin's Keto form Rather than having the “key-lock” structures as in the docking result, the simulated conformations of the Enol form showed unfit structures between the Curcumin molecule and the minor groove of DNA molecule A B C Figure 3.9 Three (A, B, C) of 101 confomations of DNA and Curcumin's Enol form 24 Master Thesis | Nguyen Thi Tuoi Hydrogen bonds analysis The hydrogen bonds of two systems were determined and filtered at donor-acceptor distances in a range 2.2-4.0 Å by Chimera software Hydrogen bonds and their distances are listed in the appendix and In Keto system, 20 conformations of 101 conformations contained hydrogen bonds of DNA and Curcumin, in which hydroxyl group in the benzene ring of Curcumin molecule always acts as a donor linked to oxygen or phosphate atoms of Cytosine nucleotide (Appendix 1) Donor-acceptor distances of the hydrogen bonds are in the 2.5-3.2 Å range, therefore the level of bonding is moderate and mostly electrostatic About Enol system, hydrogen bonds between DNA and Curcumin appeared in 34 of the 101 conformations with an average of two hydrogen bonds in a model (Appendix 2) Donor-acceptor distances of the hydrogen bonds are almost in range 2.5-3.3Å In all the conformations containing hydrogen bonds between DNA and Curcumin, the oxygen atom in the Enol group of Curcumin molecule acts as a donor whereas the oxygen atom in the Keto group is an acceptor of bonding Guanine and Thymine nucleotides of DNA molecule often contain oxygen groups that interact with the Curcumin molecule 3.2 Empirical research results 3.2.1 DNA amplification PCR products were electrophoresed on 1.5% agarose gels Images of electrophoresis showed that 410 bp PCR products were obtained in accordance with the theoretical calculations for primers designed Figure 3.10 shows bright and clear bands without secondary bands confirming no nonspecific pairing Thus, we amplified the 410 bp DNA fragment for FTIR experiments 25 Master Thesis | Nguyen Thi Tuoi Figure 3.10 Electrophoretic result of PCR product Lane M: 100bp DNA ladder Lane 1-6: PCR product Lane 7: negative control with PCR-grade water instead of DNA template 3.2.2 FTIR results Lane M: 100bp DNA ladder Lane 1-6: PCR product DNA Lane 7: negative control with PCR-grade water instead of DNA -1  3350.35 templatecm : O-H stretching vibration of the hydroxyl groups  1645.28 cm-1: C=O stretching vibration  406.98 cm-1: C-CH out-of-plane bending Lane M: 100bp DNA ladder Lane 1-6: PCR product Lane 7: negative control with PCR-grade water instead of DNA template Lane M: 100bp DNA ladder Lane 1-6: PCR product Lane 7: negative control with PCR-grade water instead of DNA template Figure 3.11 FITR image of DNA 26 Master Thesis | Nguyen Thi Tuoi Curcumin  3269.50 cm-1: O-H stretching vibration  1641.42 cm-1: C=0 stretching vibration of the carboxylic groups  1516.05 cm-1: mixed vibrations of aromatic ν(CC), ν(CCH)  424.34 cm-1 and 410.84 cm-1: -OH out-of-plane bending Figure 3.12 FTIR image of Curcumin DNA-Curcumin mixture  3257.77 cm-1: a strong broad band is due the combination of O-H stretching vibration in Curcumin and DNA structure  1635.64 and 1602.85: C=O of Curcumin and DNA  1234, 1197 cm-1: PO2- stretching of DNA  1062 cm-1 and 1064 cm-1: DNA C-O stretching Figure 3.13 FITR image of DNA-Curcumin mixture 27 Master Thesis | Nguyen Thi Tuoi The FTIR results show the spectral variation of the C = O group in the Curcumin sample compared to the DNA and Curcumin mixing sample, suggesting the formation of a new bond in the C = O group of the Curcumin in the Curcumin mixture with DNA FTIR studies were performed with samples at pH 7, at which pH Curcumin’s Enol form was more stable than Keto form Therefore, this result corresponds to the simulation result of Curcumin in the Enol form with hydrogen bonds appearing in the Keto group 28 Master Thesis | Nguyen Thi Tuoi CONCLUSION From the above results, we came to conclusions: The Curcumin’s Enol form interacts with Guanine and Thymine (GT) of the DNA in the minor groove by weak hydrogen bonds, while the previous study of Koonammackal et al who used different DNA fragment and showed that the Curcumin’s enol molecule also bound to the minor groove but in Adenine and Thymine (AT) region Our results suggest that Curcumin’s Enol form binds to minor groove of DNA molecule, but no specific nucleotides associated In Keto form, the Curcumin molecule tends to be placed outside the grooves of the DNA molecule, while hydrogen bonds are weak and occur at low frequencies The FTIR data correspond to the simulation result of Curcumin’s Enol form with a hydrogen bond appearing between the Keto group of Curcumin and DNA molecule 29 Master Thesis | Nguyen Thi Tuoi REFERENCE English [1] A Rahman, FH Stillinger "Improved simulation of liquid water by molecular dynamics." 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US EPA Retrieved 9, 2018, from Predictive Models and Tools for Assessing Chemicals under the Toxic Substances Control Act (TSCA): https://www.epa.gov/tsca-screening-tools [26] O'Neil, M (2013) The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals Royal Society of Chemistry, 474 Retrieved from toxicology data network: https://toxnet.nlm.nih.gov/ 31 Master Thesis | Nguyen Thi Tuoi APPENDIX Hydrogen bonds of DNA and Curcumin’s Keto form Model Donor 25 26 28 29 30 30 31 32 33 45 46 47 48 53 54 55 56 58 59 CUR O4’ CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 CUR O4 Acceptor Hydrogen DCYT O1P DCYT O5’ DCYT O5’ DCYT O5’ DCYT O5’ DCYT O1P DCYT O5’ DCYT O1P DCYT O5’ DCYT O5’ DCYT O5’ DCYT O1P DCYT O1P DCYT O5’ DCYT O2P DCYT O2P DCYT O2P DCYT O2P DCYT O2P DCYT O2P CUR H4’ CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 CUR H4 D A dist 2.889 3.229 3.236 2.928 3.291 2.8 3.191 2.752 2.809 3.114 3.113 3.101 2.719 2.985 2.556 2.902 2.743 2.588 3.201 2.944 D-H A dist 1.909 2.304 2.327 1.95 2.434 2.007 2.314 1.882 1.98 2.224 2.15 2.343 1.812 2.042 1.632 2.079 1.772 1.63 2.253 2.038 32 Master Thesis | Nguyen Thi Tuoi APPENDIX Hydrogen bonds of DNA and Curcumin’s Enol form Model 11 11 12 13 20 25 30 32 33 34 34 35 38 39 40 40 41 41 43 43 43 46 48 49 49 51 52 52 52 53 53 53 55 56 57 57 58 58 59 Donor CUR O16 CUR O16 CUR O16 CUR O4 CUR O16 CUR O4 CUR O4 CUR O16 CUR O16 CUR O4 CUR O16 CUR O16 CUR O4 CUR O16 CUR O16 CUR O16 DTHY N3 CUR O16 DTHY N3 CUR O16 CUR O16 CUR O4' CUR O4' DGUA N2 CUR O16 DGUA N2 CUR O16 DGUA N2 DGUA N2 CUR O16 CUR O4 DGUA N2 CUR O16 CUR O16 CUR O16 DGUA N2 DGUA N2 CUR O16 DGUA N2 CUR O16 CUR O16 Acceptor DTHY O2 DTHY O2 DTHY O2 DGUA O3' DTHY O2 DCYT O1P DGUA O3' DTHY O2 DTHY O2 DGUA O3' DTHY O2 DTHY O2 DGUA O3' DTHY O2 DTHY O2 DTHY O2 CUR O2 DTHY O2 CUR O2 DTHY O4' DCYT O4' DTHY O2 DTHY O4' CUR O2 DGUA O1P CUR O2 DCYT O3' CUR O2 CUR O2 DCYO3' DTHY O1P CUR O2 DCYT O3' DGUA O1P DCYTO3' CUR O2 CUR O2 DGUA O1P CUR O2 DGUA O1P DGUA O1P Hydrogen CUR H16 CUR H16 CUR H16 CUR H4 CUR H16 CUR H4 CUR H4 CUR H16 CUR H16 CUR H4 CUR H16 CUR H16 CUR H4 CUR H16 CUR H16 CUR H16 DTHY H3 CUR H16 DTHY H3 CUR H16 CUR H16 CUR H4' CUR H4' DGUA H21 CUR H16 DGUA H21 CUR H16 DGUA H21 DGUA H21 CUR H16 CUR H4 DGUA H21 CUR H16 CUR H16 CUR H16 DGUA H21 DGUA H21 CUR H16 DGUA H21 CUR H16 CUR H16 D A D-H A dist dist 3.732 3.06 3.371 2.868 3.787 3.254 3.478 2.632 3.967 3.168 3.105 2.251 3.418 2.584 3.934 3.332 3.768 3.131 3.683 2.887 3.605 3.031 3.603 3.048 3.561 2.644 3.14 2.649 2.605 1.846 2.784 1.873 3.264 2.46 3.094 2.258 3.539 2.851 3.37 2.715 2.717 1.718 3.939 3.145 2.958 2.098 3.87 3.016 3.834 2.901 2.903 2.229 2.944 2.099 3.635 2.792 3.23 2.273 2.885 1.899 3.114 2.351 3.285 2.434 2.858 1.995 3.191 2.336 2.946 2.186 3.907 3.007 2.822 2.056 2.865 1.897 3.1 2.132 2.675 1.771 2.751 1.805 33 Master Thesis | Nguyen Thi Tuoi 60 60 61 62 62 62 63 63 64 64 65 66 67 67 68 68 68 69 73 74 75 77 78 79 80 81 82 85 86 90 91 91 91 91 91 92 100 DGUA N2 CUR O16 CUR O16 DGUA N2 CUR O4 CUR O4 DGUA N2 CUR O16 CUR O16 CUR O4 CUR O16 CUR O16 CUR O16 CUR O4 DGUA N2 CUR O16 CUR O4 CUR O16 DGUA N2 DGUA N2 DGUA N2 DGUA N2 DGUA N2 DGUA N2 DGUA N2 DGUA N2 DGUA N2 DGUA N2 DGUA N2 CUR O4 DTHY N3 CUR O16 CUR O16 CUR O4 CUR O4 CUR O4 CUR O4 CUR O2 DGUA O1P DGUA O1P CUR O2 DADE O3' DTHY O5' CUR O16 DGUA O4' DGUA O4' DTHY O4' DGUA O4' DGUA O4' DGUA O4' DTHY O1P CUR O16 DGUA O4' DTHY O1P DGUA O4' CUR O16 CUR O16 CUR O16 CUR O16 CUR O16 CUR O16 CUR O16 CUR O16 CUR O16 CUR O16 CUR O16 DTHY O1P CUR O2 DGUA O3' DADE O5' DTHY O3' DTHY O1P DTHY O3' DTHY O1P DGUA H22 CUR H16 CUR H16 DGUA H22 CUR H4 CUR H4 DGUA H21 CUR H16 CUR H16 CUR H4 CUR H16 CUR H16 CUR H16 CUR H4 DGUA H21 CUR H16 CUR H4 CUR H16 DGUA H22 DGUA H22 DGUA H22 DGUA H22 DGUA H22 DGUA H22 DGUA H22 DGUA H22 DGUA H22 DGUA H22 DGUA H22 CUR H4 DTHY H3 CUR H16 CUR H16 CUR H4 CUR H4 CUR H4 CUR H4 3.21 2.629 3.19 3.557 3.257 3.988 3.69 2.832 3.17 2.775 2.612 2.646 2.755 2.955 2.982 2.847 2.985 2.698 2.914 3.352 2.753 3.308 2.79 2.822 2.918 2.899 2.795 2.573 2.689 3.219 6.969 7.84 7.865 3.25 3.758 3.339 2.916 2.467 1.632 2.335 2.76 2.425 3.125 2.736 1.83 2.184 1.97 1.644 1.684 1.765 2.195 2.277 1.863 2.1 1.89 2.028 2.445 1.827 2.328 1.815 1.887 2.056 2.188 1.88 1.582 1.758 2.317 6.137 7.115 7.01 2.355 2.908 2.426 2.005 34 ... application of computational tools has become increasingly useful in the study of the structure and interactions of DNA with other compounds, particularly in the design of target DNA drugs On the... theatoms donorwith and position the acceptor of hydrogen bonds, N2, distance O3, O4, O4’, H22, H4: dist.:form donor-acceptor distance.hydrogen bonds with DNA the conformation ofD A Keto showed stronger... carbonyl group of Curcumin to Nitrogen groups of Guanine of DNA molecule In 2011, the research group of Koonammackal published the study on the interaction between Curcumin’s Enol form with DNA