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Two phytochemicals, thymol and thymoquinone obtained from thymes (Thymus vulgaris L., Lamiaceae etc.) and Nagila Sativa seed, respectively. Both the phytochemicals show several biochemical activities like anticancer, antimicrobial etc. In this paper, we studied the affinities of thymol and thymoquinone towards calf thymus DNA (CT-DNA) and protein (bovine serum albumin). Spectroscopic and molecular modelling studies revealed that both compounds have a high affinity toward both the receptors; DNA and protein. Both phytochemicals binds to the minor grooves of DNA and suitable pockets of protein. Several free energy function and hydrogen bonding play significant role during the binding phenomenon. Communicated by Ramaswamy H. Sarma

Structural information about drug-receptor interactions is paramount in drug discovery and subsequent optimization processes. Drugs can bind to multiple potential targets as they contain common chemical entities in their structures. Understanding the details of such interactions offer possibilities for repurposing and developing potent inhibitors of disease pathways. Vinblastine (VLB) is a potent anticancer molecule showing multiple receptor interactions with different affinities and degrees of structural perturbations. We have investigated the multi-target binding profile of VLB with DNA and human serum albumin (HSA) in a dynamic physiological environment using spectroscopic, molecular dynamics simulations, and quantum mechanical calculations to evaluate the structural features, mode, ligand and receptor flexibility, and energetics of complexation. These results confirm that VLB prefers to bind in the major groove of DNA with some inclination toward Thymidine residue and the TR-5 binding site in HSA with its catharanthine half making important contacts with both the receptors. Spectroscopic investigation at multiple temperatures has also proved that VLB binding is entropy driven indicating the major groove and TR-5 binding site of interaction. Finally, the overall binding is facilitated by van der Waals contacts and a few conventional H-bonds. VLB portrays reasonable conformational diversity on binding with multiple receptors.

Binding of Nile Blue (NB) with calf thymus DNA has been studied using molecular modeling, spectroscopic, and thermodynamic techniques. Our study revealed that NB binds to the DNA helix by two types of modes (groove binding and intercalation) simultaneously. The thermodynamic study showed that the overall binding free energy is a combination of several negative and positive free energy changes. The binding was favored by negative enthalpy and positive entropy changes (due to the release of water from the DNA helix). The docking study validated all experimental evidence and showed that NB binds to a DNA minor groove at low concentrations and switches to intercalation mode at higher concentrations.

Formetanate Hydrochloride (FMT), a highly potent chemical, acts as an insecticide, acaricide, and miticide to protect various fruits and vegetables. The widespread use elevates concern about its presence in the ecosystem, impact upon human health via interaction with biological receptors. Spectroscopic and molecular modeling techniques at different temperatures were used to investigate the binding of FMT with Human serum albumin (HSA) at the molecular level. The experimental and computational results have provided the binding affinity, binding mode, conformational flexibility, and thermodynamic profile of FMT-HSA complex. The FMT binding appears to be spontaneous, and entropy driven. Overall binding affinity of FMT falls within -7.29 to -4.67 Kcal M-1. FMT binds in domain I, subdomain IA of HSA and is stabilized by hydrophobic interactions. Molecular dynamics simulations of the FMT-HSA complex over 100 ns at 288 K, 298 K and 308 K indicated that FMT showed minor adjustments in conformation and placement within the binding site. While, MM/PBSA analysis of the complex provided individual contributions of energy terms. Quantum mechanical (QM) calculations were used to calculate absolute energy values of different poses of FMT which in turn showed minor variations in energy suggesting slight conformational variation in the bound form. The computational results are in agreement with experimental findings.

Pictet–Spengler cyclization method has been adopted for the synthesis of three carboline derived compounds: two compounds with tetrahydro gama- and beta-having CF3 group and amino alkyl chain at delta and alpha position, respectively, and another with guanidine alkyl chain at alpha-position. Structure–activity relationship of the analogues with human serum albumin was studied by fluorescence and Fourier-transform infrared spectroscopy followed by molecular docking. The data showed maximum affinity of human serum albumin with comp7 (S0-820) followed by comp3 (S0-1040) and least with comp1 (S0-728). The compounds were tested for cytotoxic potencies. Comp3, showed maximum cytotoxicity with GI50 6.2 µM, against HCT-116, followed by comp7, and poor cytotoxicity with comp1. Comp3 and 7 induced oxidative stress mediated autophagy led programmed cell death in HCT-116. Furthermore, the compounds effectively inhibit DNA topoisomerase I activity and showed anti-inflammatory actions. In vivo studies regarding therapeutic protective action of Comp3, as a representative carboline analogue, against colon toxicant, 1,2-dimethylhydrazine dihydrochloride (DMH), showed the efficacy of the compound against organ toxicity. The existing studies on biological evaluation showed that these synthetic compounds may have a major role as anticancer agents having myriad of proven therapeutic applications. Communicated by Ramaswamy H. Sarma HighlightsStructure-activity relation showed maximum affinity of HSA with comp7 followed by comp3 and least with comp1.Comp3 and 7 induced oxidative stress mediated autophagy led programmed cell death in HCT-116.The compounds effectively inhibit DNA topoisomerase I activity and showed anti-inflammatory actionsIn vivo studies showed the efficacy of the compound against megacolon condition. Structure-activity relation showed maximum affinity of HSA with comp7 followed by comp3 and least with comp1. Comp3 and 7 induced oxidative stress mediated autophagy led programmed cell death in HCT-116. The compounds effectively inhibit DNA topoisomerase I activity and showed anti-inflammatory actions In vivo studies showed the efficacy of the compound against megacolon condition.

Evaluation of ideal sample for identification and essential to evaluate successful engraftment after hematopoietic stem cell transplantation needs a sensitive and accurate method. A successful HSCT results in complete donor derived cells in patient's hematopoiesis. The main aim of chimerism analysis is to check the concentration of donor cells which is considered as useful method for the success of treatment. The present study was carried out to determine the chimeric status of patients who underwent hematopoietic stem cell transplantation involving female patient and male donor using commercially available Y-DNA based quantification kit. This study enrolled fourteen female patients of HSCT. Samples from patient and donor were collected before transplant as reference sample. Post-transplant samples were collected from female patients after 30 days, 60 days, and 90 days of time interval. Chimeric status of the patients was analyzed using Y- DNA quantitation.

Some of the SARS-CoV-2 variants are said to be more infectious than the previous others and are causing panic around the globe. Cases related to Delta plus (δ+) and omicron (ο) variants are on the rise worldwide. This sudden surge warrants an investigation into the reasons for its binding with ACE-2. The present study attempts to find out the structural basis of binding interactions of SARS-CoV-2 mutants based on computational modeling and comparative analysis. In silico strategies including protein-protein docking, mutation analysis, molecular dynamics, and binding energy calculations were used to study the binding of the 'receptor binding domain' (RBD) of the seven ‘variants of concern’ which include Alpha (α), Beta (β), Gamma (γ), Kappa (κ), Delta (δ), Delta plus (δ+) and omicron (ο) with ACE-2 (human angiotensin-converting enzyme-2) and with antibodies. Among all the variants dealt with in this study, Delta plus and omicron were found to be binding more strongly to ACE-2 than others due to inherent mutations and the consequent change in the hydrophilic and hydrophobic environment of the binding site. Furthermore, molecular dynamic (MD) simulations and subsequent MM/PBSA calculations provided useful structural insights into key residues participating in the interaction. Infectivity of a virus could be dependent on the interplay of evading antibodies and simultaneously attaching strongly with the host receptor. A cross-correlation between mutant spike proteins' binding with ACE-2 and antibodies provides a holistic assessment of the binding nature of these mutants vis-à-vis native virus and offers opportunities for designing potential therapeutics against these new mutants. Communicated by Ramaswamy H. Sarma

Biochemical activities of Fluorescein, Rose Bengal and Rhodamine 101 were studied by DNA binding, antibacterial and cytotoxic studies. DNA binding studies were done using spectroscopic, thermodynamic and molecular modeling techniques. Antibacterial activities were investigated against a gram-negative bacteria Escherichia coli and a gram-positive bacteria Staphylococcus aureus. Cytotoxic activities were studied against Wi-38 cell line. We observed these dyes bound to minor groove of DNA and structural diversity of dyes affect the phenomenon. No significant antibacterial and cytotoxic activities of these dyes were found in our observations. Communicated by Ramaswamy H. Sarma

The work highlighted interaction of harmalol, harmaline and harmine with human serum albumin by biophysical and biochemical assays. Presence of serum protein in the media negatively affects the cyt...

Identification of an individual is the prime object in forensic case works both in civil or criminal situations like paternity/maternity disputes, sexual assaults, murder, mass disaster victims etc. STR analysis has already proved its potential to give accurate results. In addition to autosomal chromosomes, sex determination at many times is crucial in forensic situations, especially in situations like rape cases or in cases of missing persons. The chances of wrong interpretations may arise due to false detection (or non-detection) of STR fragments overall or only at amelogenin-specific fragments, in situation like mutations, intersex conditions, trans-sexualism etc., due to natural or artificial chimersim. The forensic relevance of the possible misinterpretation of STR's or amelogenin should never be underestimated. The present study was carried out to identify an individual using Y-STR in sex mismatch patients who received hematopoietic stem cell transplantation. Hematopoietic stem cell transplantation is a method to replace patient's stem cell with the stem cell donated by the donor preferably biological related in order to cure malignant and non malignant diseases. This study enrolled ten female patients of HSCT. Samples were collected as pre and post transplant after 15 days, 30 days, 60 days, and 90 days of time interval from sex mismatch patient (female) and from donor (male) and chimeric status of the patient was analyzed using Y-STR markers (23 loci). Results demonstrated that donor genotype existed in blood and buccal swab of the recipient but no genetic profile existed for Y-STR in hair follicle of the recipient. This study suggests that only hair follicle out of three biological samples tested serves as reliable source of recipient's origin after HSCT for accurate personal identification especially in forensic situations.

A simple, environmentally benign and highly proficient microwave assisted one-pot approach for the synthesis of antimicrobial spiropyrrolidine/thiapyrrolizidine oxindole derivatives is reported assembling two pharmacophoric moieties (1,3-indanedione and pyrrolidine/thiapyrrolizidine) in a single molecular framework via three-component 1,3-dipolar cycloaddition reaction of substituted isatin, sarcosine/1,3-thiazoles-4-carboxylic acid and Knoevenagel adduct (2-Cyano-3-phenyl-acrylic acid ethyl ester or 2-Benzylidene-malononitrile) in 2,2,2-trifluoroethanol as a reusable green solvent. Good functional group tolerance and broad scope of usable substrates are other prominent features of the present methodology with high degree of chemo-, regio- and stereoselectivity. The stereochemistry of synthesized compounds was confirmed by single crystal X-ray analysis. All the synthetic compounds were examined for their antimicrobial potential. The synthesized compounds having pyrrolothiazole moiety showed excellent activity against K. pneumoniae as compared to others and even more inhibitory activity than the mentioned drugs, i.e. compounds 6a (MIC=0.09μg/mL), 6b (MIC=0.045μg/mL), 6c (MIC=0.005μg/mL), 6d (MIC=0.19μg/mL). Additionally, compound 6c has shown better binding affinity against New Delhi Metallo-beta-Lactamase-1 (NDM-1) protein in computational docking studies.

The work highlighted interaction of harmalol, harmaline and harmine with human serum albumin by biophysical and biochemical assays. Presence of serum protein in the media negatively affects the cytotoxicity of the alkaloids. MTT assay indicates concentration-dependent growth inhibitory effect of the alkaloids on A375, MDA-MB-231, HeLa, A549, ACHN and HepG2 cell, having maximum cytotoxicity with GI50 value of 6.5 μM on ACHN by harmine in 1% of fetal bovine serum. Detail cytotoxic studies on ACHN cell by harmine, the most cytotoxic among the three, reveal nucleosomal fragmentation, formation of comet tail, generation of reactive oxygen species, decreased mitochondrial membrane potential, up regulation of p53, caspase 3 and significant increase in G2/M population that made the cancer cells prone to apoptosis. Furthermore, the findings unequivocally pointed out that harmine binds strongly to the protein with a binding constant of 5.53 × 104 M−1 followed by harmaline and least with harmalol. Thermodynamic results revealed enthalpy dominated, entropy favored, 1:1 binding. Molecular docking and circular dichroism suggested changed conformation of protein by partial unfolding on complexation. Further supported by infrared analysis where protein secondary structure was altered with a major decrease of α-helix from 53.68% (free protein) to 8–11% and change in β-sheet from 25.31% (free protein) to 1–6% upon binding, inducing partial protein destabilization. Site markers demonstrated site I (subdomain IIA) binding of the alkaloids to the protein. The results serve as data for the future development of serum protein-based targeted drugs. AbbreviationsCD: circular dichroism; FBS: fetal bovine serumFRETForster resonance energy transferFTIRFourier transform infraredHSAhuman serum albumin; ROS: reactive oxygen species CD: circular dichroism; FBS: fetal bovine serum Forster resonance energy transfer Fourier transform infrared human serum albumin; ROS: reactive oxygen species Communicated by Ramaswamy H. Sarma

In this paper, the interaction of rhodamine123 (R123) with calf thymus DNA has been studied using molecular modeling and other biophysical methods like UV-vis spectroscopy, fluoremetry, optical melting, isothermal titration calorimetry, and circular dichroic studies. Results showed that the binding energy is about -6 to -8 kcal/mol, and the binding process is favored by both negative enthalpy change and positive entropy change. A new method to determine different thermodynamic properties like calorimetric enthalpy and heat capacity change has been introduced in this paper. The obtained data has been crossed-checked by other methods. After dissecting the free-energy contribution, it was observed that the binding was favored by both negative hydrophobic free energy and negative molecular free energy which compensated for the positive free energies due to the conformational change loss of rotational and transitional freedom of the DNA helix.

Here we report a murder/paternity case with an incompatibility at locus D3S1358. Examination of 24 autosomal loci revealed no mismatches with a high paternity index. Since the questioned child was a male & the Y-chromosome is transmitted exclusively to the male lineage we studied a battery of 25 Y-STR's in the child & father. Since the battery of autosomal &Y chromosomal STR's employed confirmed the paternity & maternity, the observed incompatibility or mismatch could be due to a mutational event.

We report the identification of skeletal remains using DNA technology. DNA was isolated from severely decomposed human remains using pre-extraction decalcification followed by optimized phenol/chloroform DNA extraction procedure. Additionally DNA from the reference samples of the relatives was extracted using the Automate Express DNA extraction system. Quantifiler™ Human DNA quantification kit was used for DNA quantification. AmpFl STR Identifiler plus PCR amplification kit was used to simultaneously amplify 15 autosomal Short Tandem Repeat (STR) loci alongwith the gender specific locus amelogenin.

DNA technology has been exemplified as a mighty development in forensic science. The forensic utility of DNA profiling technique has proved to be a cutting edge in the field of molecular genetics. We present two cases selected from our routine casework performed at FSL Delhi that comprise of difficult forensic samples viz. soft and hard tissues. These cases were solved using DNA technology with increased number of autosomal and Y chromosomal markers. The technology aided not only to nab the accused but also to exonerate the suspect and is no doubt a boon to the investigating agencies

The present study explores the use of 15 STR loci D8S1179, D21S11, D7S820, CSF1PO, D3S1358, THO1, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, FGA in addition to a gender identification marker, amelogenin in forensic investigation & paternity testing.

Short tandem repeat (STR) profiles generated from 1160 individuals generated by the Identifiler plus PCR amplification kit were screened for variant alleles not represented within the manufacturer's provided allelic ladder. A total of ten (10) distinct variants were observed at 2 of the 15 loci namely D13S317 & FGA. These alleles strengthen the genetic evidence in trouble some cases & increase the range of alleles.

Binding of Rhodamine B to Calf thymus DNA (CT DNA) was studied using various biophysical techniques and molecular docking method. Circular dichroic studies revealed that conformation of CT DNA changed moderately and unwind on binding with Rhodamine B. The binding was cooperative in nature. The overall binding constant, evaluated from Benesi Hidebrand plot was seen to be in the range of 103 M−1. Salt dependence binding data showed that the binding free energy depends on salt concentration. From the thermodynamics studies, it was concluded that binding process is favored by both negative enthalpy change and positive entropy change. Molecular docking calculations and Quenching experiment confirmed that the dye binds in the minor groove of CT DNA. These results further advance our knowledge on the molecular aspects on the interaction of these types of dyes to nucleic acids.

Molecular docking, molecular mechanics, molecular dynamics and relaxation matrix simulation protocols have been extensively used to generate the structural details of ligand-receptor complexes in order to understand the binding interactions between the two entities. Experimental methods like NMR spectroscopy and X-ray crystallography are known to provide structural information about ligand-receptor complexes. In addition, fluorescence spectroscopy, circular dichroism (CD) spectroscopy and molecular docking have also been utilized to decode the phenomenon of the ligand-DNA interactions, with good correlation between experimental and computational results. The DNA binding affinity was demonstrated by analysing fluorescence spectral data. Structural rigidity of DNA upon ligand binding was identified by CD spectroscopy. Docking is carried out using the DNA-Dock program which results in the binding affinity data along with structural information like interatomic distances and H-bonding, etc. The complete structural analyses of various drug-DNA complexes have afforded results that indicate a specific DNA binding pattern of these ligands. It also exhibited that certain structural features of ligands can make a ligand to be AT- or GC-specific. It was also demonstrated that changing specificity from AT base pairs to GC base pairs further improved the DNA topoisomerase inhibiting activity in certain ligands. Thus, a specific molecular recognition signature encrypted in the structure of ligand can be decoded and can be effectively employed in designing more potent antiviral and antitumour agents.

The interaction of two natural protoberberine plant alkaloids berberine and palmatine with tRNA phe was studied using various biophysical techniques and molecular modeling and the data were compared with the binding of the classical DNA intercalator, ethidium. Circular dichroic studies revealed that the tRNA conformation was moderately perturbed on binding of the alkaloids. The cooperative binding of both the alkaloids and ethidium to tRNA was revealed from absorbance and fluorescence studies. Fluorescence quenching studies advanced a conclusion that while berberine and palmatine are partially intercalated, ethidium is fully intercalated on the tRNA molecule. The binding of the alkaloids as well as ethidium stabilized the tRNA melting, and the binding constant evaluated from the averaged optical melting temperature data was in agreement with fluorescence spectral-binding data. Differential scanning calorimetry revealed that the tRNA melting showed three close transitions that were affected on binding of these small molecules. Molecular docking calculations performed showed the preferred regions of binding of these small molecules on the tRNA. Taken together, the results suggest that the binding of the alkaloids berberine and palmatine on the tRNA structure appears to be mostly by partial intercalation while ethidium intercalates fully on the tRNA. These results further advance our knowledge on the molecular aspects on the interaction of these alkaloids to tRNA.

RNA has attracted recent attention for its key role in gene expression and targeting by small molecules for therapeutic intervention. This work focuses towards understanding interaction of harmalol, a DNA intercalator, with RNAs of different motifs viz. single-stranded A-form poly(A), double-stranded A-form of poly(C)·poly(G), and clover leaf tRNAphe by different spectroscopic, calorimetric, and molecular modeling techniques. Results of this study converge to suggest that (i) binding constant varied in the order poly(C)·poly(G) > tRNAphe > poly(A), (ii) non-cooperative binding of harmalol to poly(C)·poly(G) and poly(A) and cooperative binding with tRNAphe, (iii) significant structural changes of poly(C)·poly(G) and tRNAphe with concomitant induction of optical activity in the bound achiral alkaloid molecules, while with poly(A) no induced Circular dichroism (CD) perturbation was observed, (iv) the binding was predominantly exothermic, enthalpy-driven, entropy-favored with poly(C)·poly(G), while it was entropy driven with tRNAphe and poly(A), (v) a hydrophobic contribution and comparatively large role of non polyelectrolytic forces to Gibbs energy changes with poly(C)·poly(G) and tRNAphe and (vi) intercalated state of harmalol inside poly(C)·poly(G) structure as revealed from molecular docking was supported by the viscometric and ferrocyanide quenching data. All these findings unequivocally pointed out that harmalol prefers binding with poly(C)·poly(G), compared to tRNAphe and poly(A); this results serve as data for the development of RNA-based antiviral drugs. This work focuses to understand the interaction of harmalol with RNAs of different motifs viz. single-stranded A-form poly(A), double-stranded A-form of poly(C)·poly(G) and clover leaf tRNAphe by different spectroscopic, and calorimetric techniques, and molecular docking methods. The findings unequivocally point out that harmalol prefers to bind strongly to poly(C)·poly(G) in an intercalative mode, compared to a weak binding to tRNAphe and poly(A). The results may serve in the design of RNA-targeted antiviral drugs.

The work focuses towards interaction of harmaline, with nucleic acids of different motifs by multispectroscopic and calorimetric techniques. Findings of this study suggest that binding constant varied in the order single-stranded (ss) poly(A) > double-stranded calf thymus (CT) DNA > double-stranded poly(G)·poly(C) > clover leaf tRNAPhe . Prominent structural changes of ss poly(A), CT DNA, and poly(G)· poly(C) with concomitant induction of optical activity in the bound achiral alkaloid molecule was observed, while with tRNAPhe , very weak induced circular dichroism perturbation was seen. The interaction was predominantly exothermic, enthalpy driven, and entropy favored with CT DNA and poly(G)·poly(C), while it was entropy driven with poly(A) and tRNAPhe . Intercalated state of harmaline inside poly(A), CT DNA, and poly(G)·poly(C) was shown by viscometry, ferrocyanide quenching, and molecular docking. All these findings unequivocally pointed out preference of harmaline towards ss poly(A) inducing self-structure formation. Furthermore, harmaline administration caused a significant decrease in proliferation of HeLa and HepG2 cells with GI50 of 28μM and 11.2μM, respectively. Nucleic acid fragmentation, cellular ultramorphological changes, decreased mitochondrial membrane potential, upregulation of p53 and caspase 3, generation of reactive oxygen species, and a significant increase in the G2 /M population made HepG2 more prone to apoptosis than are HeLa cells.

Background Base dependent binding of the cytotoxic alkaloid harmalol to four synthetic polynucleotides, poly(dA).poly(dT), poly(dA-dT).poly(dA-dT), poly(dG).poly(dC) and poly(dG-dC).poly(dG-dC) was examined by various photophysical and calorimetric studies, and molecular docking. Methodology/principal findings Binding data obtained from absorbance according to neighbor exclusion model indicated that the binding constant decreased in the order poly(dG-dC).poly(dG-dC)>poly(dA-dT).poly(dA-dT)>poly(dA).poly(dT)>poly(dG).poly(dC). The same trend was shown by the competition dialysis, change in fluorescence steady state intensity, stabilization against thermal denaturation, increase in the specific viscosity and perturbations in circular dichroism spectra. Among the polynucleotides, poly(dA).poly(dT) and poly(dG).poly(dC) showed positive cooperativity where as poly(dG-dC).poly(dG-dC) and poly(dA-dT).poly(dA-dT) showed non cooperative binding. Isothermal calorimetric data on the other hand showed enthalpy driven exothermic binding with a hydrophobic contribution to the binding Gibbs energy with poly(dG-dC).poly(dG-dC), and poly(dA-dT).poly(dA-dT) where as harmalol with poly(dA).poly(dT) showed entropy driven endothermic binding and with poly(dG).poly(dC) it was reported to be entropy driven exothermic binding. The study also tested the in vitro chemotherapeutic potential of harmalol in HeLa, MDA-MB-231, A549, and HepG2 cell line by MTT assay. Conclusions/significance Studies unequivocally established that harmalol binds strongly with hetero GC polymer by mechanism of intercalation where the alkaloid resists complete overlap to the DNA base pairs inside the intercalation cavity and showed maximum cytotoxicity on HepG2 with IC50 value of 14 µM. The results contribute to the understanding of binding, specificity, energetic, cytotoxicity and docking of harmalol-DNA complexation that will guide synthetic efforts of medicinal chemists for developing better therapeutic agents.

Vinblastine (VLB), a cytotoxic alkaloid is used extensively against various cancer types and the crystal structure of its tubulin complex is already known. Multitarget affinity of vinblastine has been investigated and the nature of binding with biological receptors namely, duplex DNA and Human serum albumin (HSA) has been compared to the binding characteristics of its known complex with natural high affinity receptor tubulin using molecular docking and QM-MM calculations. VLB is found to interact with DNA as well as HSA protein, though, with weaker affinity as compared to tubulin. Analysis of various docked complexes revealed that the H-bonds and cation-pi bonds do not have significant contribution to the binding interactions and despite its large size, VLB remains in relaxed conformation and fits in the hydrophobic regions on the receptors.

Fluorescence studies on the indole alkaloids vinblastine sulfate, vincristine sulfate, vincamine and catharanthine have demonstrated the DNA binding ability of these molecules. The binding mode of these molecules in the minor groove of DNA is non-specific. A new parameter of the purine-pyrimidine base sequence specificty was observed in order to define the non-specific DNA binding of ligands. Catharanthine had shown ‘same’ pattern of ‘Pu-Py’ specificity while evaluating its DNA binding profile. The proton resonances of a DNA decamer duplex were assigned. The models of the drug:DNA complexes were analyzed for DNA binding features. The effect of temperature on the DNA binding was also evaluated.

Identification of the structure of DNA is an important step towards understanding its function in various biochemical processes. X-ray crystallography and NMR are the two most important tools for the evaluation of the structure of the DNA double helix. The present work employs NMR method to identify the structural details of the DNA oligomer sequences. 2D 1H NOESY experiments were used to find out the chemical shift values of each cross peak. Complete structural assignment was furnished for DNA oligomers using 2D-NOESY technique. The cross peak volumes obtained from most of the NOESY peaks clearly indicated that most of the nucleotides in the DNA oligomer were in the B-form with a few residues in the A-form conformation. All the nucleotides were shown to have anti-conformation of deoxyribose sugar with respect to the nuclear base.

DNA binding drugs form an important class of compounds which can be utilized as anticancer and antibacterial agents. We have investigated the DNA binding ability of small indole derivatives using fluorescence and molecular docking techniques. The results clearly demonstrate that small indole derivatives bind with DNA double helix showing binding affinity of 104–105 per mole. All the indole derivatives were found to be binding in the minor groove of DNA. The binding was non-specific nature and dominated by van der Waals and hydrophobic forces. The experimental and computational results were found to be in good agreement as evident by the high correlation constant values.

Interaction of the protoberberine alkaloid coralyne with t-RNA(phe) was investigated using various biophysical techniques. Results of absorption and fluorescence studies revealed that the alkaloid binds to t-RNA exhibiting positive cooperativity. Isothermal titration calorimetry results suggested that the binding of the alkaloid was predominantly enthalpy driven with a smaller favourable entropy term. A surprisingly large favourable component for non-electrostatic contribution to the binding of coralyne to t-RNA was revealed from salt dependence data and the dissection of the free energy. The alkaloid enhanced the thermal stability of t-RNA and the binding affinity values obtained from optical thermal melting data was in agreement with that from calorimetry. The heat capacity change of -125 cal mol(-1) K(-1) and the observed significant enthalpy-entropy compensation phenomenon confirmed the involvement of multiple weak noncovalent interactions. Circular dichroism studies provided evidence for significant perturbation of the t-RNA structure with concomitant induction of optical activity in the bound achiral alkaloid molecules. Binding isotherms generated from circular dichroic data confirmed the cooperative binding mode of the alkaloid as deduced from spectroscopic data. Docking studies provided further insights into the partially intercalated state of coralyne inside the t-RNA structure. This study presents a complete binding and thermodynamic profile of coralyne interaction to t-RNA.

Eight indole derivatives were studied for their DNA binding ability using fluorescence quenching and molecular docking methods. These indole compounds have structural moieties similar as in few indole alkaloids. Experimental and theoretical studies have suggested that indole derivatives bind in the minor groove of DNA. Thermodynamic profiles of DNA complexes of indole derivatives were obtained from computational methods. The complexes were largely stabilized by H-bonding and van der Waal’s forces with positive entropy values. Indole derivatives were found to possess some Purine (Pu) — Pyrimidine (Py) specificity with DNA sequences. The results obtained from experimental and computational methods showed good agreement with each other, supported by their correlation constant values.