Interacting Amino Acid Residues Research Articles

Kajian Molecular Docking Senyawa Quercetin dari Buah Terong Pokak (Solanum torwum Swartz) sebagai Antiinflamasi pada Protein Tumor Necrosis Factor-α (TNF-α)

Quercetin is a polyphenolic flavonoid with potential chemopreventive activity. Quercetin is a chemical compound found in Solanum torvum Sw fruit. Quercetin is one of the compounds that are considered to have anti-inflammatory effects. Inflammation is a localized protective response elicited by tissue damage caused by physical trauma, damaging chemicals, or microbiology. Tumor Necrosis Factor-α (TNF-α) is a proinflammatory cytokine that functions in mediating the innate immune response. Irregular production of cytokines can lead to various immunopathological conditions, including auto-inflammatory, autoimmune, and cancer-causing diseases. This study aims to determine the potential of quercetin compounds derived from turkey berry (Solanum torvum Sw.) which have the potential as anti-inflammatory drugs with parameters such as ∆G, the interaction of residues on TNF-α protein (PDB ID: 6X85) with molecular docking, and pharmacophore studies using Lipinski, pkCSM, and SwissADME filters. The molecular docking simulation results showed that the quercetin compound had a ∆G value of -8.55 kcal/mol and had amino acid residue interactions in the form of ILE155; TYR59; GLY121; TYR119; GLN61; TYR151; VAL123; LEU157; ILE58; GLY122; SER60; LEU120; LEU157. Quercetin has the potential as an anti-inflammatory drug on TNF- α protein with an LD50 value of 2.471; bioavailability value of 0.55; does not have hepatotoxicity and skin sensitization properties and has passed the Lipinski test.

Quantum chemical calculations, spectroscopic studies and molecular docking investigations of the anti-cancer drug quercitrin with B-RAF inhibitor

Quercitrin is an anti-lung cancer agent. It is a naturally occurring flavonoid and its derivatives are mainly present in nuts and beverages. It is mainly available as a glycoside, and the quercitrin glycosides are found to prevent the metastasis of cancer. Quercitrin is optimized with 6–311++G(d,p) basis set using the B3LYP method to attain its minimum energy structure. The vibrational studies of the Quercitrin compound were elucidated with reference to Potential Energy Distribution (PED). The geometrical parameters were obtained and correlated with experimental values. To examine the nature of the charge transfer mechanism of Quercitrin, the HOMO-LUMO energy gap is computed. The anti-cancer activity of Quercitrin has been explored using molecular docking study that are used to estimate how the ligand interacts with protein, specifically to identify the best-fit orientation of the ligand, its binding mode, and intermolecular interactions of amino acid residues in the binding region of B-RAF kinase protein. The binding affinity of the compound Quercitrin (-7.14 kcal/mol) was found using AutoDock and validated with a Glide XP score in Schrodinger tool (-8.01 kcal/mol). MD simulations of protein-ligand complexes were monitored for 100 ns, from which the RMSD, RMSF, Rg, H-bonds, and interaction energy calculations were executed. From these investigations, it is identified that the compound quercitrin has maintained good structural stability, compactness, higher Hydrogen bonds, and interaction energies than the Imidazopyridinyl benzamide inhibitor.

In Silico Studies on The Potential of Green Tea Catechin Compounds (Camellia sinensis) as Antiviral of SARS CoV-2 Againts Spike Glycoprotein (6LZG) and Main Protease (5R7Y)

COVID-19 is a disease caused by SARS CoV-2 by producing structural proteins and non-structural proteins. SARS CoV-2 uses a spike glycoprotein to bind ACE-2 receptors in host cells and uses main protease to replicate. This research aims to screen green tea catechin derivates as an antiviral for SARS CoV-2 through inhibition of spike glycoprotein (6LZG) and main protease (5R7Y). In silico studies carried out are molecular docking, prediction of physicochemical properties, and prediction of toxicity. The potential inhibition was assessed based on binding affinity and interaction of amino acid residues. From the molecular docking process showed that epicatechin and epigallocatechin provide inhibition to spike glycoprotein better than nafamostat indicated by binding affinity of -5.2 kcal/mol and -4.5 kcal/mol, while epigallocatechin gallate and epicatechin gallate provide inhibiton to main protease better than lopinavir with binding affinity of -8.7 kcal/mol and -8.3 kcal/mol. The results of the physicochemical properties prediction showed that only epigallocatechin gallate that did not fulfill five Lipinski's rule. Based on the toxicity class LD50, the derivates of catechin belong to classes 4 and 6. In conclusion, it can be known that epicatechin and epigallocatechin can be developed as an antiviral for SARS CoV-2.

The potency of blumeatin and luteolin as caspase-1 inhibitor by molecular docking

COVID-19 infection induces inflammation by increasing cytokines such as IL-1b, IL-6, IL-18, IFN-γ, and TNF-α. IL-1b is generated by the involvement of caspase-1. Therefore, caspase-1 inhibitor can be potential for inflammation therapy caused by COVID-19 infection. This study aims to determine the potential of blumeatin and luteolin as anti-inflammatory agents by inhibiting caspase-1 using a molecular docking approach. This study was carried out by caspase-1 (PDB ID: 1RWK) preparation, blumeatin and luteolin structure optimization, docking protocol validation, and docking of blumeatin and luteolin on caspase-1. Bluematin and luteolin had a binding affinity of -5,63 kcal/mol and -5,93 kcal/mol, lower than Q158 native ligand (-3.92 kcal/mol). Similar amino acid residues in hydrogen bonds interaction were observed between Q158 native ligand, blumeatin, and luteolin with caspase-1 (GLN 283 and ARG 179). Blumeatin and luteolin are potentially anti-inflammation agents through the inhibition of the caspase-1 in silico.

Phytoestrogens as Potential Antiandrogenic Agents Against Prostate Cancer: An In Silico Analysis

Background: Prostate cancer is the second most common cancer worldwide. The androgen deprivation therapy or castration leads to the recurrence of castration-resistant prostate cancer after some time. Androgen receptor is one of the most promising targets for the treatment of prostate cancer. The health benefits of phytoestrogens led us to explore them for their androgen receptor inhibition potential that may lead to inhibition of initiation and progression of prostate cancer. Methods: Protein-ligand interaction plays a central role in structure-based drug design, so we screened 23 phytoestrogens for their binding affinity to the androgen receptor using the molecular docking approach. These phytoestrogens were also tested for their ADME and toxicity profiles using the software. Results: Based on binding affinity, interacting amino acid residues, pharmacokinetics and toxicity profile, four phytoestrogens, namely naringenin, luteolin, hesperetin, and biochanin A were shortlisted as lead molecules. Conclusion: Therefore, our study has shown that these four phytoestrogens could be promising candidates for further evaluation for prostate cancer treatment or management.

Structural binding perspectives of common plasticizers and a flame retardant, BDE-153, against thyroxine-binding globulin: potential for endocrine disruption.

The human exposure to diverse endocrine-disrupting chemicals (EDCs) has increased dramatically over several decades with very adverse health effects. Plasticizers and flame retardants constitute important classes of EDCs interfering in endocrine physiology including the thyroid function. Thyroxine (T4) is an important hormone regulating metabolism and playing key roles in developmental processes. In this study, six phthalate and nonphthalate plasticizers and one flame retardant (BDE-153) were subjected to structural binding against thyroxine-binding globulin (TBG). The aim was to understand their potential role in thyroid dysfunction using structural binding approach. The structural study was performed using Schrodinger's induced fit docking, followed by binding energy estimations of ligands and the molecular interaction analysis between the ligands and the amino acid residues in the TBG ligand-binding pocket. The results indicated that all the compounds packed tightly into the TBG ligand-binding pocket with similar binding pattern to that of TBG native ligand, T4. A high majority of TBG interacting amino acid residues for ligands showed commonality with native ligand, T4. The estimated binding energy values were highest for BDE-153 followed by nonphthalate plasticizer, DINCH, with values comparable with native ligand, T4. The estimated binding energy values of other plasticizers DEHP, DEHT, DEHA, ATBC, and TOTM were less than DINCH. In conclusion, the tight docking conformations, amino acid interactions, and binding energy values of the most of the indicated ligands were comparable with TBG native ligand, T4, suggesting their potential for thyroid dysfunction. The results revealed highest potential thyroid disruptive action for BDE-153 and DINCH.

A novel laccase-based biocatalyst for selective electro-oxidation of 2-thiophene methanol

An effective biocatalyst was fabricated for TEMPO-mediated electrooxidation of 2-thiophene methanol. Laccase obtained from Trametes versicolor was covalently immobilized onto electrochemically polymerized ortho-amino benzoic acid (PABA) layer on carbon fiber paper (CFP) electrode. The composite material was characterized by Fourier transformed infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), Optical profilometry (OP), and scanning electron microscopy (SEM). Electrochemical parameters were studied using cyclic voltammetry (CV). Moreover, the developed biocatalyst (Lac-PABA/CFP) was used for selective conversion of 2-thiophene methanol to 2-thiophene carboxaldehyde using 2,2,6,6-Tetramethyl-1-piperidinyloxy, free radical (TEMPO) as a mediator. The formation of the product was confirmed via FTIR, GCMS–, 1HNMR and 13CNMR. The enzyme activity of free and immobilized laccase was studied using 2, 2′-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) substrate at optimal conditions. Computational In silico analysis also suggested the presence of active sites (T2/T3 trimeric sites-copper ions) in laccase (PDB id: 1KYA’s) interacting amino acid residues with the TEMPO and 2-thiophene methanol. Additionally, molecular dynamics simulations revealed that 2-thiophene methanol as compared to TEMPO is more stable (better RMSD, RMSF) in interacting with laccase specifically having strong interaction residues at Asp206, Glu242, Gly262, Gln293, and Glu302. Furthermore, the proposed strategy was confirmed by assessing the various interactions using computational tools. This work would be highly beneficial to develop an electrocatalyst for effective synthesis of 2-thiophene carboxaldehyde, a common intermediate in pharmaceutical, agrochemical, dye, fertilizer and chemical industries.

Interaction of various types of bisphenols with enzymes involved in melanin synthesis

ObjectivesBisphenol is one of the commercial chemical compounds which finds application in the manufacture of phenol, polyesters, polycarbonates, epoxy resins, etc. Bisphenol A is the most commonly found bisphenol derivative, although there are various analogues such as Bisphenol S, Bisphenol B, Bisphenol C, Bisphenol E, Bisphenol AF, which vary with their structures. Bisphenols majorly get into us by means of food as they are found in food packaging and beverage containers and can be easily absorbed by the body. They can make way into the body systems either by direct means like skin contact or by indirect means through food that is stored in a bisphenol-coated containers. Exposure of the human system to this compound may bring about mild to adverse ailments ranging from skin irritations to infertility. Pigmentation disorder is one such health condition that occurs due to melanocyte destruction and is caused by bisphenol exposures. They interact with various proteins and enzymes that have been involved in the melanocyte synthesis pathway, thereby disrupting their normal functions.MethodsIn silico analysis has been done to predict the interaction and other descriptive binding parameters when the bisphenol derivatives BPA. BPB, BPC, BPE, BPS and BPAF have been docked with some of the essential proteins for melanin synthesis such as tyrosinase, tyrosinase-related protein 1(TRP-1), dopachrome tautomerase/tyrosinase-related protein-2(TRP-2).ResultsThe interaction has been quantified with the binding energies, and the interacting amino acid residues have also been identified. The results showed strong interactions for both the proteins TRP-1 and TRP-2 with BPA. BPB, BPC, BPE, BPS and BPAF.ConclusionsThe risk and threats caused by the commercial products made of bisphenol are at higher levels, and thereby, the need for a safe and desirable alternative has been insisted.

Identification of Potential Scaffolds From the Shrub Justicia Adhatoda Against SARS-CoV-2 Main Protease Target

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious and pathogenic virus. To date, there is a lack of proper medication against this virus, which has triggered the scientific community to find therapeutics. Searching of SARS-CoV-2 main protease inhibitors from anti-viral natural products based on traditional knowledge may be an effective approach. In this work, structure-based virtual screening of the compounds of Justicia adhatoda was performed against SARS-CoV-2 Mpro, followed by ADME filtration, molecular dynamics, and MMGBSA-based binding free energy calculation. On the basis of docking score, crucial interacting amino acid residues, molecular dynamics, and binding energy profile, three novel phenolic compounds JA_38b, JA_38c, and JA_39 were selected as potential binders against SARS-CoV-2 Mpro. This information may be used to develop potential therapeutics countermeasures against SARS-CoV-2 infection after in vitro and detailed pharmacological study.

In silico prediction of phytoconstituents from Ehretia laevis targeting TNF-α in arthritis

ObjectiveRheumatoid arthritis (RA) is an autoimmune disease involving the synovial lining of the major joints. Current therapies have noteworthy side effects. Our study involved in silico evaluation of Ehretia laevis (E. laevis) phytoconstituents targeting tumor necrosis factor-α (TNF-α). MethodsMolecular docking studies performed to investigate the binding pattern of the plant E. laevis phytoconstituents along with the crystal structure of TNF-α (PDB ID: 2AZ5) using AutoDock Vina followed by a study of interacting amino acid residues and their influence on the inhibitory potentials of the active constituents. Further the pharmacokinetic profile and toxicity screening carried out using SwissADME and pkCSM. ResultsThe docked results suggest that lupeol (− 9.4 kcal/mol) and α-amyrin (− 9.4 kcal/mol) has best affinity towards TNF-α compared to standard drug thalidomide (− 7.4 kcal/mol). The active chemical constituents represents better interaction with the conserved catalytic residues, leading to the inhibition/blockade of the TNF-α-associated signaling pathway in RA. Furthermore, pharmacokinetics and toxicity parameters of these phytochemicals were within acceptable limits according to ADMET studies. ConclusionThe binding potential of phytoconstituents targeting TNF-α showed promising results. Nonetheless, it encourages the traditional use of E. laevis and provides vital information on drug development and clinical treatment.

GC-MS- and NMR-Based Metabolomics and Molecular Docking Reveal the Potential Alpha-Glucosidase Inhibitors from Psychotria malayana Jack Leaves.

Psychotria malayana Jack leaf, known in Indonesia as “daun salung”, is traditionally used for the treatment of diabetes and other diseases. Despite its potential, the phytochemical study related to its anti-diabetic activity is still lacking. Thus, this study aimed to identify putative inhibitors of α-glucosidase, a prominent enzyme contributing to diabetes type 2 in P. malayana leaf extract using gas chromatography-mass spectrometry (GC-MS)- and nuclear magnetic resonance (NMR)-based metabolomics, and to investigate the molecular interaction between those inhibitors and the enzyme through in silico approach. Twenty samples were extracted with different solvent ratios of methanol–water (0, 25, 50, 75, and 100% v/v). All extracts were tested on the alpha-glucosidase inhibition (AGI) assay and analyzed using GC-MS and NMR. Multivariate data analysis through a partial least square (PLS) and orthogonal partial square (OPLS) models were developed in order to correlate the metabolite profile and the bioactivity leading to the annotation of the putative bioactive compounds in the plant extracts. A total of ten putative bioactive compounds were identified and some of them reported in this plant for the first time, namely 1,3,5-benzenetriol (1); palmitic acid (2); cholesta-7,9(11)-diene-3-ol (3); 1-monopalmitin (4); β-tocopherol (5); α-tocopherol (6); 24-epicampesterol (7); stigmast-5-ene (8); 4-hydroxyphenylpyruvic acid (10); and glutamine (11). For the evaluation of the potential binding modes between the inhibitors and protein, the in silico study via molecular docking was performed where the crystal structure of Saccharomyces cerevisiae isomaltase (PDB code: 3A4A) was used. Ten amino acid residues, namely ASP352, HIE351, GLN182, ARG442, ASH215, SER311, ARG213, GLH277, GLN279, and PRO312 established hydrogen bond in the docked complex, as well as hydrophobic interaction of other amino acid residues with the putative compounds. The α-glucosidase inhibitors showed moderate to high binding affinities (−5.5 to −9.4 kcal/mol) towards the active site of the enzymatic protein, where compounds 3, 5, and 8 showed higher binding affinity compared to both quercetin and control ligand.

A Mathematical Graph-Theoretic Model of Single Point Mutations Associated with Sickle Cell Anemia Disease

Many diseases like cystic fibrosis and sickle cell anemia disease (SCD), among others, arise from single point mutations in the respective proteins. How a single point mutation might lead to a global devastating consequence on a protein remains an intellectual mystery. SCD is a genetic blood-related disorder resulting from mutations in the beta chain of the human hemoglobin protein (simply, β-globin), subsequently affecting the entire human body. Higher mortality and morbidity rates have been reported for patients with SCD, especially in sub-Saharan Africa. Clinical management of SCD often requires specialized interdisciplinary clinicians. SCD presents a major global burden, hence an improved understanding of how single point mutations in β-globin results in different phenotypes of SCD might offer insight into protein engineering, with potential therapeutic intervention in view. By use of mathematical modeling, we built a hierarchical (nested) graph-theoretic model for the β-globin. Subsequently, we quantified the network of interacting amino acid residues, representing them as molecular system of three distinct stages (levels) of interactions. Using our nested graph model, we studied the effect of virtual single point mutations in β-globin that results in varying phenotypes of SCD, visualized by unsupervised machine learning algorithm, the dendrogram.

Investigation of major amino acid residues of anti-norfloxacin monoclonal antibodies responsible for binding with fluoroquinolones

It is important to understand the amino acid residues that govern the properties of the binding between antibodies and ligands. We studied the binding of two anti-norfloxacins, anti-nor 132 and anti-nor 155, and the fluoroquinolones norfloxacin, enrofloxacin, ciprofloxacin, and ofloxacin. Binding cross-reactivities tested by an indirect competitive enzyme-linked immunosorbent assay indicated that anti-nor 132 (22–100%) had a broader range of cross-reactivity than anti-nor 155 (62–100%). These cross-reactivities correlated with variations in the numbers of interacting amino acid residues and their positions. Molecular docking was employed to investigate the molecular interactions between the fluoroquinolones and the monoclonal antibodies. Homology models of the heavy chain and light chain variable regions of each mAb 3D structure were docked with the fluoroquinolones targeting the crucial part of the complementarity-determining regions. The fluoroquinolone binding site of anti-nor 155 was a region of the HCDR3 and LCDR3 loops in which hydrogen bonds were formed with TYR (H:35), ASN (H:101), LYS (H:106), ASN (L:92), and ASN (L:93). These regions were further away in anti-nor 132 and could not contact the fluoroquinolones. Another binding region consisting of HIS (L:38) and ASP (H:100) was found for norfloxacin, enrofloxacin, and ciprofloxacin, whereas only ASP (H:100) was found for ofloxacin.

In silico, theoretical biointerface analysis and in vitro kinetic analysis of amine compounds interaction with acetylcholinesterase and butyrylcholinesterase

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are considered important target for drug design against Alzheimer's disease. In the present study in silico analysis; theoretical analysis of biointerface between ligand and interacting amino acid residues of proteins; and in vitro analysis of enzyme inhibition kinetics were carried out to delineate the inhibitory property of amine compounds against AChE/BChE. High throughput virtual screening of amine compounds identified three compounds (2-aminoquinoline, 2-aminobenzimidazole and 2-amino-1-methylbenzimidazole) that best interacted with AChE/BChE. Molecular docking analysis revealed the interaction of these compounds in the active site gorge of AChE/BChE, in particular with amino acid residues present in the peripheral anionic site. Molecular dynamics simulation confirmed the stable binding of these compounds with AChE/BChE. Binding energy calculated through MMGBSA method identified the non-covalent interactions (electrostatic and Van der Waals interactions) have contributed to the stable binding of the amine compounds with the AChE/BChE. Biointerface between amine compounds and AChE/BChE were visualized through Hirshfeld surface analysis. The inter-fragment interaction energies for the possible contacts between amine compounds and amino acid residues were carried out for the first time. All the amine compounds showed mixed-type of inhibition with moderate Ki value in in vitro analysis.

In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol.

Phlorotannins are polyphenolic compounds in marine alga, especially the brown algae. Among numerous phlorotannins, dieckol and phlorofucofuroeckol-A (PFF-A) are the major ones and despite a wider biological activity profile, knowledge of the G protein-coupled receptor (GPCR) targets of these phlorotannins is lacking. This study explores prime GPCR targets of the two phlorotannins. In silico proteocheminformatics modeling predicted twenty major protein targets and in vitro functional assays showed a good agonist effect at the α2C adrenergic receptor (α2CAR) and an antagonist effect at the adenosine 2A receptor (A2AR), δ-opioid receptor (δ-OPR), glucagon-like peptide-1 receptor (GLP-1R), and 5-hydroxytryptamine 1A receptor (5-TH1AR) of both phlorotannins. Besides, dieckol showed an antagonist effect at the vasopressin 1A receptor (V1AR) and PFF-A showed a promising agonist effect at the cannabinoid 1 receptor and an antagonist effect at V1AR. In silico molecular docking simulation enabled us to investigate and identify distinct binding features of these phlorotannins to the target proteins. The docking results suggested that dieckol and PFF-A bind to the crystal structures of the proteins with good affinity involving key interacting amino acid residues comparable to reference ligands. Overall, the present study suggests α2CAR, A2AR, δ-OPR, GLP-1R, 5-TH1AR, CB1R, and V1AR as prime receptor targets of dieckol and PFF-A.

Inhibitory effect of naturally occurring Ocimum sanctum extract on α-Synuclein aggregation in aqueous solution

α-Synuclein (α-Syn) has a propensity to form amyloids and is one of the major causes of neurodegenerative disorders like Parkinson’s disease (PD). Despite a lot of research, there is no obviating therapy available for PD and related disorders. Therefore, discovering new inhibitors against α-Syn aggregation is a subject of intense research. Against this backdrop, we have investigated the attenuating effect of naturally occurring Ocimum sanctum (OS) against aggregation in aqueous solution using various biochemical and biophysical studies. In this report, Thioflavin (ThT) and Congo red binding assays have shown the hindering effect of OS extract on β-sheet formation in α-Syn, and eventually leading to inhibition of aggregation. ANS binding assay indicated its modulatory effect on hydrophobic patches of α-Syn protein. SDS-PAGE, turbidity measurement, and light scattering assays indicated the role of OS extract in increasing protein solubility. Morphological studies conducted by TEM and DLS suggested that OS extract prevents the formation of large fibrils. This work also extends to reveal the inhibitory and disaggregation effects of OS extract on A53T mutant induced aggregation and pre-existing fibrils respectively. Also, MTT assay implied the protective effect of OS extract on neuroblastoma cells against fibril induced cytotoxicity. Furthermore, docking studies of α-Syn with different molecules of OS extract navigated for putative interacting amino acid residues. Thus, due to the presence of polyphenolic compounds, OS extract binds with α-Syn and inhibits its aggregation. This study implicates that OS extract and associated molecules may become a potential therapeutic intervention against PD and other aggregation related disorders.

Structures of two novel crystal forms of Aspergillus oryzae alpha amylase (taka-amylase)

The structures of Aspergillus oryzae α-amylase were determined in a tetragonal crystal, having one molecule as asymmetric unit, and a monoclinic crystal with two molecules as asymmetric unit. Both crystal forms were obtained from trace contaminants of an old commercial lipase preparation. Structures were determined and refined to 1.65Å and 1.43Å resolution respectively. The latter crystal has a non-crystallographic (NCS) twofold axis within the asymmetric unit. Glycosylation at Asn197 is evident, and in the tetragonal crystal can be seen to include three, partially disordered sugar residues following the initial N-acetyl glucosamine (NAG). Superposition of the tetragonal crystal model on the α-amylases from Bacillus subtilis (PDB:1BAG), pig pancreas (PDB:3L2L), and barley (PDB:1AMY), show a high degree of coincidence, particularly for the (β/α)8-barrel domains, and especially within the active site. Using this structural agreement between amylases, we extrapolated the binding model of a six residue, limit dextrin found in pig pancreas α-amylase to the A.oryzae enzyme model, which predicts substrate interacting amino acid residues.

Introducing a two‐dimensional graph of docking score difference vs. similarity of ligand‐receptor interactions

Observation of molecular docking results was generally performed by analyzing the docking score and the interacting amino acid residues separately either in tables or graphs. Sometimes it was not easy to rank the tested ligands’ docking results, especially if there were many ligands. This study aims to introduce a new way to analyze docking results with a two‐dimensional graph between the difference in docking score and the similarity of ligand‐receptor interactions. Molecular docking was performed with one reference ligand and several test ligands. The docking score difference was obtained between the test and the reference ligands as the graph’s x‐axis. Meanwhile, the y‐axis contains the similarity of ligand‐receptor interactions, obtained from the ratio of amino acid residues and the types of interactions between the test and reference ligands. Docking result analysis was more straightforward because two critical parameters were presented in one graph. This graph could be used to support the analysis of the docking results.

Biochemical evaluation and molecular docking studies on encapsulated astaxanthin for the growth inhibition of Mycobacterium tuberculosis

Astaxanthin,, a tetraterpenoid compound was formulated as liposomes and screened for anti-tubercular activity against different strains of Mycobacterium tuberculosis: MTB, MDR-TB and H37Rv isolated from the patient sputum samples. Minimum inhibitory concentration (MIC) was determined by proportion-based method. The molecular docking analysis of astaxanthin with various mycobacterial drug target proteins were performed using in silico tools. Encapsulated astaxanthin showed better inhibition of M. tuberculosis with MIC value of 500μg/mL against all the selected strains. The docking analysis provided the interacting amino acid residues of selected mycobacterial enzymes and mode of ligand-protein interaction. Based on the present study, it was concluded that encapsulated astaxanthin could be a better cost effective natural compound for the treatment of tuberculosis among the patients which will combat side effects in comparison with the first line AntiTB drugs like rifampicin and isoniazid.

Endocrine Disruption: Structural Interactions of Androgen Receptor against Di(2-ethylhexyl) Phthalate and Its Metabolites.

Diethylhexyl phthalate (DEHP) is a commonly used plasticizer in the manufacture of polyvinyl chloride plastics for household and commercial use. DEHP is a ubiquitous ecocontaminant and causes developmental and reproductive problems in children and adults. After exposure, DEHP is metabolized by endogenous hydrolysis and oxidation into the primary metabolite, mono-(2-ethylhexyl) phthalate (MEHP), and the secondary metabolites, mono-(2-ethyl-5-hydroxhexyl)phthalate (5-OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5-oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5-cx-MEPP), and mono-[(2-carboxymethyl)hexyl] phthalate (2-cx-MMHP). Very few studies have been reported on the adverse effects of DEHP metabolites, and the available information indicates that the metabolites might also be equally or more active as compared to the parent compound. In the present study, induced fit docking was used for structural binding characterization of the above five DEHP metabolites with androgen receptor (AR) to predict the potential endocrine-disrupting effects of these metabolites in AR signaling. All the DEHP metabolites interacted with the ligand-binding pocket of AR forming amino-acid residue interactions, hydrogen bonding, and pi-pi interactions. The binding energy of DEHP with AR was similar to that of native ligand testosterone. The amino-acid residue interactions of DEHP metabolites had 91–100% similarity compared to that of testosterone. In addition, all the DEHP metabolites and testosterone showed a common hydrogen bonding interaction with amino-acid Arg-752 of AR. Taken together, the structural binding data in the present study suggested the potential for DEHP metabolites to disrupt AR signaling, which may lead to androgen-related reproductive dysfunction.