Molecular Modeling Approach Research Articles

Peptidic Compound as DNA Binding Agent: In Silico Fragment-based Design, Machine Learning, Molecular Modeling, Synthesis, and DNA Binding Evaluation.

Cancer remains a global burden, with increasing mortality rates. Current cancer treatments involve controlling the transcription of malignant DNA genes, either directly or indirectly. DNA exhibits various structural forms, including the G-quadruplex (G4), a secondary structure in guanine-rich regions. G4 plays a crucial role in cellular processes by regulating gene expression and telomerase function. Researchers have recently identified G4-stabilizing binding agents as promising anti-cancer compounds. Additionally, peptides have emerged as effective anticancer pharmaceuticals due to their ability to form multiple hydrogen bonds, electrostatic interactions, and van der Waals forces. These properties enable peptides to bind to specific areas of DNA chains selectively. However, despite these advancements, designing G4-binding peptides remains challenging due to a lack of comprehensive information. In our present study, we employed an in silico fragment-based approach to design G4- binding peptides. This innovative method combines machine learning classification, molecular docking, and dynamics simulation. AutoDock Vina and Gromacs performed molecular docking and MD simulation, respectively. The machine learning algorithm was implemented by Scikit-learn. Peptide synthesis was performed using the SPPS method. The DNA binding affinity was measured by applying spectrophotometric titration. As a result of this approach, we identified a high-scoring peptide (p10; sequence: YWRWR). The association constant (Ka) between p10 and the ctDNA double helix chain was 4.45 × 105 M-1. Molecular modeling studies revealed that p10 could form a stable complex with the G4 surface. The obtained Ka value of 4.45 × 105 M-1 indicates favorable interactions. Our findings highlight the role of machine learning and molecular modeling approaches in designing new G4-binding peptides. Further research in this field could lead to targeted treatments that exploit the unique properties of G4 structures.

Correlation between in vitro anti-urease activity and in silico molecular modeling approach of novel imidazopyridine–oxadiazole hybrids derivatives

Abstract In the current era, a potent drug is still needed on the market for the treatment of various diseases worldwide. Researchers mainly focus on those enzymes that cause these diseases. One of the major diseases is caused by an enzyme called urease, which increases the concentration of ammonia in the body upon hydrolysis. Researchers across the globe have keen interest to synthesize the potent inhibitor for this conversion. From this perspective, hybrid analogs of imidazopyridine and oxadiazole (1–20) were designed and efficiently synthesized followed by characterizing them through varied spectroscopic methods (1HNMR, 13CNMR, and HREI-MS). In addition, in vitro analyses of the synthesized compounds were conducted to evaluate their anti-urease potency. There was significant potential in most compounds analyzed, but analogs 15, 16, and 17 (IC50 = 2.20 ± 0.10 μM, IC50 = 2.50 ± 0.10 μM, and IC50 = 2.30 ± 2.10 μM, respectively) performed exceptionally well in comparison with thiourea (IC50 = 22.30 ± 0.44 μM). The selected candidates were further investigated under a molecular docking study to confirm protein ligand interactions. In addition, energy gap (E gap) of the HOMO–LUMO was explored via density functional theory studies.

Comparative study on interactions of phillyrin and phillygenol with lysozyme: Spectroscopy, differential scanning calorimetry and molecular modeling approaches

Phillyrin (PR) and its derivative phillygenol (PG) are major active extracts of the Chinese medicine Forsythiae Fructus. Lysozyme, an important carrier protein, has a variety of physiological along with pharmaceutical functions. Herein, the interactions of PR and PG with hen egg white lysozyme (HEWL) are investigated in details by spectroscopic analyses, differential scanning calorimetry (DSC) tests, and molecular modeling approaches. Fluorescence measurement and UV–visible absorption difference spectroscopy reveal that an “untypical static quenching” takes place pointing towards the formation of ground state complex. The binding constants of HEWL-PG are greater than that of HEWL-PR. Moreover, the major driving force for the binding process is elucidated as hydrophobic interactions for both cases. Circular dichroism spectroscopy and three-dimensional fluorescence indicate that PR and PG decrease the helical structure of the HEWL and hydrophobicity surrounding Trp and Tyr residues. The thermal stability of HEWL decreases in the presence of PR and PG by DSC. Docking study infers that both PR and PG could bind to the hydrophobic cavity of HEWL and supports the higher binding of PG than PR. Molecular dynamics study illustrates that PR has higher relative position change, which may attribute to its lower binding ability. In terms of the radius of gyration (Rg), PG causes the protein structure to swell even more. The average hydrogen bonds number of HEWL-PG is less than that of HEWL-PR and more changes of the residual fluctuation are observed in HEWL-PG system. Furthermore, MM-PBSA analysis exhibits that HEWL-PG has lower binding energy. Collectively, these results support that both PR and PG could bind to HEWL, but PG possesses higher affinity which leads to stronger secondary structural changes of HEWL than PR. These findings are beneficial to comprehensively understand the binding characteristic of PR and PG with HEWL, providing experimental basis for pharmacokenitics of PR and PG.

Ocular pharmacological and biochemical profiles of 6-thioguanine: a drug repurposing study.

The purine analog 6-thioguanine (6TG), an old drug approved in the 60s to treat acute myeloid leukemia (AML), was tested in the diabetic retinopathy (DR) experimental in vivo setting along with a molecular modeling approach. A computational analysis was performed to investigate the interaction of 6TG with MC1R and MC5R. This was confirmed in human umbilical vein endothelial cells (HUVECs) exposed to high glucose (25mM) for 24h. Cell viability in HUVECs exposed to high glucose and treated with 6TG (0.05-0.5-5µM) was performed. To assess tube formation, HUVECs were treated for 24h with 6TG 5µM and AGRP (0.5-1-5µM) or PG20N (0.5-1-5-10µM), which are MC1R and MC5R antagonists, respectively. For the in vivo DR setting, diabetes was induced in C57BL/6J mice through a single streptozotocin (STZ) injection. After 2, 6, and 10weeks, diabetic and control mice received 6TG intravitreally (0.5-1-2.5mg/kg) alone or in combination with AGRP or PG20N. Fluorescein angiography (FA) was performed after 4 and 14weeks after the onset of diabetes. After 14weeks, mice were euthanized, and immunohistochemical analysis was performed to assess retinal levels of CD34, a marker of endothelial progenitor cell formation during neo-angiogenesis. The computational analysis evidenced a more stable binding of 6TG binding at MC5R than MC1R. This was confirmed by the tube formation assay in HUVECs exposed to high glucose. Indeed, the anti-angiogenic activity of 6TG was eradicated by a higher dose of the MC5R antagonist PG20N (10µM) compared to the MC1R antagonist AGRP (5µM). The retinal anti-angiogenic effect of 6TG was evident also in diabetic mice, showing a reduction in retinal vascular alterations by FA analysis. This effect was not observed in diabetic mice receiving 6TG in combination with AGRP or PG20N. Accordingly, retinal CD34 staining was reduced in diabetic mice treated with 6TG. Conversely, it was not decreased in diabetic mice receiving 6TG combined with AGRP or PG20N. 6TG evidenced a marked anti-angiogenic activity in HUVECs exposed to high glucose and in mice with DR. This seems to be mediated by MC1R and MC5R retinal receptors.

Identification of Antiviral Phytocompounds as Potential Anti‐Dengue Agents against DENV NS2B/NS3 Protease: An Integrated Molecular Modelling and Dynamics Approach

AbstractDengue fever is one of the most dreaded viral diseases caused by the bite of female Aedes aegypti and Aedes albopictus mosquitoes infected with the Dengue virus (DENV). No DENV antiviral drugs have been approved, yet they are desperately needed. The current study focuses on finding potential therapeutics from 8 medicinal plants reported to have activity against the DENV NS2B/NS3 protease in vitro. Eighty‐two phytocompounds were selected from eight different medicinal plants like Vernonia cinerea, Tridax procumbens, Cassia angustifolia, Lawsonia inermis, Dryobalanops aromatic, Punica granatum, Zingiber zerumbet and Zizyphus‐jujuba. The top five phytocompounds (Epicatechin (EPI), Chrysoeriol (CHR), Apigenin (API), Quercetin‐3,4′‐Dimethylether (QUE), and Caffeic acid (CAF)) identified from toxicity evaluation and docking studies were further subjected to 100 ns long Molecular Dynamics (MD) simulations to study their structural stability and binding affinity through MM‐PBSA based free‐energy calculations. MD results revealed overall conformational stability with all the five phytocompounds. Furthermore, MM‐PBSA results suggest binding free energy values of −154.415 kJ/mol, −151.154 kJ/mol, −139.048 kJ/mol, −122.827 kJ/mol), and −120.622 kJ/mol for compound EPI, QUE, API, CAF, and CHR respectively by interacting with essential binding site residues. These compounds could thus be studied extensively to develop nature‐based therapeutic compounds as anti‐dengue agents for DENV2.

2-hydrazinobenzothiazole based derivatives: Synthesis, characterization, antifungal, DNA binding and molecular modelling approaches

In this study, eleven new 2-hydrazinobenzothizole derivatives (Z1–Z11) were synthesized by condensation reaction. The molecular structure of the derivatives was confirmed using FT-IR, NMR, and mass spectrometry. The heterocyclic derivatives (Z1–Z11) were tested for their in vitro antifungal activity against the fungal strains C. albicans, C. glabrata, and C. tropicalis. The outcomes showed that heterocyclic analog Z5, with a MIC value of 450μM, demonstrates noteworthy activity against strain C. tropicalis, while Z7 displays antifungal activity against C. tropicalis, with MIC values of 480μM. When compared to the common medication fluconazole. Ct-DNA binding studies of both lead compounds were carried out using UV–visible, fluorescence, and cyclic voltammetry (CV) measurements. Results from the binding study depicted that the compounds demonstrated a groove mode of binding. In addition, molecular docking analysis of the ligand molecules with PDBID: 5FSA revealed numerous interactions, strong binding, and a high MM/GBSA score, indicating a stable complex. Furthermore, a 100ns molecular dynamics (MD) simulation demonstrated minimal deviation and fluctuations, along with significant intermolecular interactions, further confirming the stability of the complex.

Exploration of newly synthesized azo-thiohydantoins as the potential alkaline phosphatase inhibitors via advanced biochemical characterization and molecular modeling approaches

In the current study, Azo-Thiohydantoins derivatives were synthesized and characterized by using various spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR, elemental and HRMS analysis. The compounds were evaluated for alkaline phosphatase activity and it was observed that among all the synthesized compounds, derivative 7e exhibited substantial inhibitory activity (IC50 = 0.308 ± 0.065 µM), surpassing the standard inhibitor (L–Phenyl alanine, IC50 = 80.2 ± 1.1 µM). Along with this, these derivatives were comprehensively examined regarding the electronic properties and reactivity of the synthesized compounds using Density Functional Theory (DFT) calculations, where the results were found very promising and the synthesized compound were found stable. After that, SwissADME evaluations highlighted compounds for their favorable physicochemical properties, including solubility and drug-likeness. Molecular docking exhibited the strong binding affinities of 7f and 7e derivatives with intestinal alkaline phosphatase (IAP), further supported by Molecular Dynamics (MD) simulations. This comprehensive integration of experimental and computational approaches sheds the light on the potential therapeutic applications of the synthesized compounds. By providing a detailed investigation of these aspects, this research opens the avenues for the development of novel pharmacologically active compounds with diverse applications.

Molecular modelling approaches can reveal the Molecular interactions established between antimalarial targets of hemozoin pathway and the organic phytochemicals of Artocarpus species.

Ayurveda, the traditional Indian medical system, has potential applications in early malaria treatment. In an in silico docking study, 50 phytochemicals from two plants Artocarpus lakoocha Roxb. (AL) And Artocarpus heterophyllus Lam. (AH), were examined for their interactions with anti-malarial proteins (PDB IDs: 3BWK, 3BPF, 1LF3). The nucleotide analogue Artemisinin, a current malaria treatment, served as a positive control. Result showed that phytochemicals from AL and AH exhibited binding affinities as high as -9.6 kcal/mol, respectively. Additionally, molecular dynamics simulation for Artocarpin: 3BPF demonstrated stable complexes over 100 ns. Notably, Artocarpin and Quercetin displayed higher binding affinities (up to -9.6 as well as -9.5 kcal/mol, respectively) compared to Artemisinin (-7.5 up to kcal/mol), have shown. Pharmacokinetic predictions indicated the compounds were likely non-carcinogenic, water-soluble and biologically safe. In-vitro analysis using β-Hematin assay supported these findings, suggesting the phytochemicals as Hemozoin pathway inhibitors.

Selectivity of N(2)-substituted oxotriazinoindole aldose reductase inhibitors is determined by the interaction pattern with Pro301-Arg312 loop of aldehyde reductase

Novel oxotriazinoindoles (OTIs) were recently reported as highly efficient and selective aldose reductase inhibitors. Here, a series of novel N(2)-substituted oxotriazinoindoles was developed with the aim to investigate molecular interactions within the aldose reductase (ALR2) inhibitor binding site. About twice increased inhibition efficacy of the most efficient derivative 14 (N(2)-CH2CH2COOH) compared to the unsubstituted lead OTI was obtained, yet at the expense of selectivity relative to anti-target aldehyde reductase (ALR1). To explain the major drop in selectivity, observed also in other N(2)-substituted derivatives, in silico molecular modeling approach revealed the role of extra interactions with the residues of Arg309, Arg312 and Met302 located in the additional C-terminal loop of ALR1 missing in ALR2, which can prevent or enhance binding in ALR1. These key findings will be used for development of the next generation of selective OTI inhibitors.

Potential Inhibitors from Natural Compounds against SARS‐CoV‐2 Main Protease: A Systematic Molecular Modelling Approach

AbstractThe COVID‐19 outbreak poses a significant threat to the world‘s human population in 2020. Finding new drugs rapidly during this pandemic is quite challenging. Thus, in silico drug screening experiments may provide effective therapeutic alternatives for better assessing natural remedies in preventing and treating COVID‐19. The main protease (Mpro) is an important drug target that is essential and ubiquitous for the survival of SARS‐CoV‐2. In this study, we performed in silico high‐throughput virtual screening to identify potential hits employing a database of 3 million natural compounds (supernatural‐II database). The initially obtained top 100 virtual hits were subjected to a standard SP and XP docking protocol, achieving the top 30 hits. Compounds SN00340755 (glide score: −16.0 kcal/mol and ΔGbind: −134.29 kcal/mol) and SN00213037 (glide score: −13.30 kcal/mol and ΔGbind: −81.18 kcal/mol) exhibited significant binding energy against Mpro (PDB ID: 6XQS). The ligands SN00340755 and SN00213037 formed multiple hydrogen bonds with the catalytic residues, especially with the functionally important residue GLU166, which plays a significant role in protomer dimerization. Further post‐docking minimization studies (MM‐GBSA) were performed to estimate the ligand‐protein affinity. From MM‐GBSA studies, it was observed that Coulombic (−140.70 to −37.66 kcal/mol) and van der Waals (−79.32 to −20.59 kcal/mol) energies, favoring the binding of ligands to the Mpro target protein. The ADMET properties were predicted using Qikprop, Chem Axon, and Data Warrior tools, demonstrating the beneficial pharmacokinetic parameters of these natural compounds. The 100 ns molecular dynamics simulation study revealed minor protein fluctuations, indicating the stability of the protein‐ligand complex.

Identification of potential focal adhesion kinase (FAK) inhibitors: a molecular modeling approach

Focal adhesion kinase (FAK) is an enzyme of paramount importance as it is involved in several critical roles, which are linked to proliferation of cancer cells. FAK is quintessential for cancer cell mitigation, adhesion and survival, downregulation of which interferes with the growth of cancer cells. The expression of FAK is elevated in breast cancer, hepatocellular carcinomas, neuroblastoma cells, demonstrating the need for FAK inhibitors as a potential treatment. Based on an in silico drug screen, the study aimed to identify potential FAK inhibitors. 3180 molecules retrieved from the Zinc database comprising biogenic molecules, FDA-approved drugs and compounds in clinical trials were screened against the FAK enzyme (PDB:2ETM). The XP docking study of the best 51 ligands revealed that ZINC02033589 (Silymarin) showed good binding to FAK with −10.97 kcal/mol dock score followed by ZINC00518397 with −8.23 kcal/mol and ZINC03831112 − 8.07 kcal/mol. The interactions of the top three ligands with FAK were further validated by molecular dynamic simulation study of 100 ns and MM-GBSA calculations. The ΔG of binding of ZINC02033589, ZINC00518397 and ZINC03831112 was found to be −59.09, −45.08 and −48.53 kcal/mol respectively. The study established the fact that among the three molecules, ZINC02033589 showed good stability and binding towards FAK. These results could usher in the development of potential FAK inhibitor entities, that could be persuaded and substantiated by the molecules identified in this study for subsequent synthetic and bioactivity research studies. Communicated by Ramaswamy H. Sarma

Development of Potential Inhibitors for Human T-lymphotropic virus type I Integrase enzyme: A molecular modeling approach.

Integration of viral DNA into the host cell genome, carried out by the HTLV-1 integrase enzyme, is a crucial step in the Human T-lymphotropic virus type I (HTLV-1) life cycle. Thus, HTLV-1 integrase is considered an attractive therapeutic target; however, no clinically effective inhibitors are available to treat HTLV-1 infection. Objective The main objective was to identify potential drug-like compounds capable of effectively inhibiting HTLV-1 integrase activity. In this study, a model of HTLV-1 integrase structure and three integrase inhibitors (dolutegravir, raltegravir, and elvitegravir as scaffolds) were used for designing new inhibitors. Designed molecules were used as templates for virtual screening to retrieve new inhibitors from PubChem, ZINC15, and ChEMBL databases. Drug-likeness and docked energy of the molecules were investigated using the SWISS-ADME portal and GOLD software. The stability and binding energy of the complexes were further investigated using molecular dynamic (MD) simulation. Four novel potential inhibitors were developed using a structure-based design protocol and three compounds from virtual screening. They formed hydrogen bonding interactions with critical residues Asp69, Asp12, Tyr96, Tyr143, Gln146, Ile13, and Glu105. In addition, π stacking, halogen, and hydrogen bond interactions were seen between compounds (especially halogenated benzyl moieties) and viral DNA similar to those seen in parent molecules. MD simulation confirmed higher stability of the receptor-ligand complex than the ligand-free enzyme. Combing structure-based design and virtual screening resulted in identifying three drug-like molecules (PubChem CID_138739497, _70381610, and _140084032) that are suggested as lead compounds for developing effective drugs targeting HTLV-1 integrase enzyme.

Exploring crucial structural attributes of quinolinyl methoxyphenyl sulphonyl-based hydroxamate derivatives as ADAM17 inhibitors through classification-dependent molecular modelling approaches

ABSTRACT A Disintegrin and Metalloproteinase 17 (ADAM17), a Zn2+-dependent metalloenzyme of the adamalysin family of the metzincin superfamily, is associated with various pathophysiological conditions including rheumatoid arthritis and cancer. However, no specific inhibitors have been marketed yet for ADAM17-related disorders. In this study, 94 quinolinyl methoxyphenyl sulphonyl-based hydroxamates as ADAM17 inhibitors were subjected to classification-based molecular modelling and binding pattern analysis to identify the significant structural attributes contributing to ADAM17 inhibition. The statistically validated classification-based models identified the importance of the P1' substituents such as the quinolinyl methoxyphenyl sulphonyl group of these compounds for occupying the S1' - S3' pocket of the enzyme. The quinolinyl function of these compounds was found to explore stable binding of the P1' substituents at the S1' – S3' pocket whereas the importance of the sulphonyl and the orientation of the P1' moiety also revealed stable binding. Based on the outcomes of the current study, four novel compounds of different classes were designed as promising ADAM17 inhibitors. These findings regarding the crucial structural aspects and binding patterns of ADAM17 inhibitors will aid the design and discovery of novel and effective ADAM17 inhibitors for therapeutic advancements of related diseases.

Identification of dual-target isoxazolidine-isatin hybrids with antidiabetic potential: Design, synthesis, in vitro and multiscale molecular modeling approaches

In the development of novel antidiabetic agents, a novel series of isoxazolidine-isatin hybrids were designed, synthesized, and evaluated as dual α‐amylase and α-glucosidase inhibitors. The precise structures of the synthesized scaffolds were characterized using different spectroscopic techniques and elemental analysis. The obtained results were compared to those of the reference drug, acarbose (IC50 = 296.6 ± 0.825 μM for α‐amylase & IC50 = 780.4 ± 0.346 μM for α-glucosidase). Among the title compounds, 5d exhibited impressive α-amylase and α-glucosidase inhibitory activity with IC50 values of 30.39 ± 1.52 μM and 65.1 ± 3.11 μM, respectively, followed by 5h (IC50 = 46.65 ± 2.3 μM; IC50 = 85.16 ± 4.25 μM) and 5f (IC50 = 55.71 ± 2.78 μM; IC50 = 106.77 ± 5.31 μM). Mechanistic studies revealed that the most potent derivative 5d bearing the chloro substituent attached to the oxoindolin-3-ylidene core, and acarbose, are a competitive inhibitors of α-amylase and α-glucosidase, respectively. Structure activity relationship (SAR) was examined to guide further structural optimization of the most appropriate substituent(s). Moreover, drug-likeness qualities and ADMET prediction of the most active analogue, 5d was also performed. Subsequently, 5d was subjected to molecular docking and dynamic simulation during the progression of 120 ns analysis to check the essential ligand-receptor patterns, and to estimate its stability. In silico studies were found in good agreement with the in vitro enzymatic inhibitions results. In conclusion, we demonstrated that most potent compound 5d could be exploited as dual potential inhibitor of α-amylase and α-glucosidase for possible management of diabetes.

Incorporating pH into DFT-D+U and microflotation recovery studies on heterocyclic collector-pyrite interactions

This study adopted both computational and experimental approaches to design by modification of 2-mercaptobenzothiazole (MBT), 2-mercaptobenzoxazole (MBO) and 2-mercaptobenzimidazole (MBI) heterocyclic collectors by introducing a carbon sulphide (–CS2) group and forming 2-trithiocarbonatebenzothiazole (TTCBT), 2-trithiocarbonatebenzoxazole (TTCBO) and 2-trithiocarbonatebenzomidazole (TTCBI) derivatives collectors. The adsorption behaviour of the heterocyclic collectors (and derivatives) on pyrite and subsequent hydrophobicity at different pH conditions were characterised using molecular modelling and microflotation approaches, respectively. The computational adsorptions were performed on dry and hydrated surfaces in their neutral thiolate and thione (acidic) form on the pyrite (100) surface. It was found that under dry and neutral conditions the TTCBONa and TTCBTNa were more exothermic, while under dry and acidic conditions the TTCBIH was more exothermic followed by MBIH and MBTH. Under hydrated and neutral conditions MBONa was predicted as the most exothermic, while for hydrated and acidic conditions MBTH, TTCBTH and TTCBIH were more exothermic. It was found that under acidic conditions, the heterocyclic collectors were more exothermic than for neutral condition on the hydrated surface. The microflotation at pH = 8 showed that MBO achieved higher recoveries, while at pH = 6 MBT, TTCBT and TTCBI achieved higher recoveries that could reach 90 %. The derivatives under acidic conditions were found to have good recovery performance, which showed that the introduction of a –CS2 group on the exocyclic sulphur atom improved the affinity and therefore hydrophobicity of the mercapto-heterocyclic collectors on the pyrite surface, and thus these derivatives can enhance the flotation of pyrite minerals. In addition, the computational predictions complimented by experimental recoveries are essential to a meaningful development of modelling as a tool in mineral processing reagent design.

Atypical crystal growth within the supercritical antisolvent process: Experimental and molecular modeling approach with sodium bicarbonate

This paper presents the recrystallization of sodium bicarbonate (NaHCO3) using the Supercritical AntiSolvent process. The focus is pointed toward crystal habit and its modification induced by varying the solvent nature. The observed habit is uncommon with crystals exhibiting a “zigzag” shape. High Resolution Scanning Electron Microscopy observations refuted that this shape was due to particle attachment: those “zigzag” particles are likely monocrystals grown in a diffusion-limited media. Firstly, a molecular modeling study shed light on organic solvents that can interact strongly with NaHCO3 crystals. Such solvents were found to be ethylene glycol and glycine, in contrast to ethanol or water which likely interact weakly with NaHCO3 crystals. An experimental campaign confirmed the predicted interactions. Ethylene glycol interactions with NaHCO3 crystals led to the production of a different crystal salt. Alternatively, adding glycine as a growth inhibitor led to the initial polymorphic form, although with a modified growth mechanism.

Detangling Solvatochromic Effects by the Effective Fragment Potential Method.

Understanding molecular interactions in complex systems opens avenues for the efficient design of new materials with target properties. Energy decomposition methods provide a means to obtain a detailed picture of intermolecular interactions. This work introduces a molecular modeling approach for decomposing the solvatochromic shifts of the electronic excited states into the contributions of the individual molecular fragments of the environment surrounding the chromophore. The developed approach is implemented for the QM/EFP (quantum mechanics/effective fragment potential) model that provides a rigorous first-principles-based description of the electronic states of the chromophores in complex polarizable environments. On the example of two model systems, water pentamer and hydrated uracil, we show how the decomposition of the solvatochromic shifts into the contributions of individual solvent water molecules provides a detailed picture of the intermolecular interactions in the ground and excited states of these systems. The analysis also demonstrates the nonadditivity of solute-solvent interactions and the significant contribution of solute polarization to the total values of solvatochromic shifts.

Evaluating the Relative Efficacy of Synthetic and Natural Drugs in Endometriosis Adopting Molecular Modelling Approach

Background: Endometriosis is a chronic inflammatory condition of high incidence and with serious consequences. Several synthetic compounds proved to be useful in treating its symptoms by inhibiting aromatase, which is responsible for the pathogenesis of this painful illness. Nevertheless, synthetic drugs inflict several side effects, including headaches, osteoporosis, and so on. This scenario advocates the search for therapeutic formulations based on natural compounds. Thus, the present study was hypothesized to evaluate the comparative efficacy of the synthetic and natural drugs used in endometriosis, using the bioinformatics approach. Methods: CB-Dock was employed to perform molecular docking of the aromatase enzyme with two synthetic and three natural drugs for predicting their molecular interactions, and binding affinities. The curcumin-aromatase complex was further subjected to MD simulations to determine its stability, and to apply it to natural compound-based computer-aided drug discovery. Results: Curcumin was observed to dock with a greater binding interaction with aromatase. The RMSD profile, hydrogen bonds, and the RMSF and Rg values of the complex were stabilised after 50 ns, which was an indicator of the stable binding pose of the curcumin-aromatase complex. Conclusion: These in-silico findings are the basis for proposing that curcumin can be considered as a potential binding agent to inhibit the aromatase enzyme in the treatment of endometriosis. Molecular modelling and dynamics results suggest that curcumin and aromatase form a stable complex and that curcumin can be targeted as a drug in the treatment of endometriosis

Biophysical and thermodynamical insights into the interaction of mefenamic acid with human serum albumin, based on combined multi-spectroscopic and molecular modeling approaches

Biophysical and thermodynamical insights into the interaction of mefenamic acid with human serum albumin, based on combined multi-spectroscopic and molecular modeling approaches

Physicochemical and Structural Investigation of L-Threonine/Glycerol-based Deep Eutectic Solvent Using Experimental and Molecular Modelling Approaches.

One of the most popular topics in sustainable chemistry has been the creation of new eco-friendly solvents. Deep eutectic solvents (DES) have established themselves as accessible and affordable substitutes for...