Interaction Of Molecules Research Articles

Spermine and spermidine SI-PPCs: Molecular dynamics reveals enhanced biomolecular interactions

In this paper the effects on the interaction of highly positively charged substitution-inert platinum polynuclear complexes (SI-PPCs) with negatively charged DNA and heparin are examined and compared by theoretical chemistry methods. Electrostatic and hydrogen bonding interactions contribute to the overall effects on the biomolecule. Root Mean Square (RMS) deviation, Solvent Accessible Surface, RMS fluctuation, and interaction analysis all confirm similar effects on both biomolecules, dictated predominantly by the total positive charge and total number of hydrogen bonds formed. Especially, changes in structural parameters suggesting condensation and reduction of available surface area will reduce or prevent normal protein recognition and may thus potentially inhibit biological mechanisms related to apoptosis (DNA) or reduced vascularization viability (HEP). Thermodynamic analyses supported these findings with favourable interaction energies. The comparison of DNA and heparin confirms the general intersectionality between the two biomolecules and confirms the intrinsic dual-nature function of this chemotype. The distinction between the two-limiting mode of actions (HS or DNA-centred) could reflect an intriguing balance between extracellular (GAG) and intracellular (DNA) binding and affinities. The results underline the need to fully understand GAG-small molecule interactions and their contribution to drug pharmacology and related therapeutic modalities. This report contributes to that understanding.

Impact of protein and small molecule interactions on kinase conformations.

Protein kinases act as central molecular switches in the control of cellular functions. Alterations in the regulation and function of protein kinases may provoke diseases including cancer. In this study we investigate the conformational states of such disease-associated kinases using the high sensitivity of the kinase conformation (KinCon) reporter system. We first track BRAF kinase activity conformational changes upon melanoma drug binding. Second, we also use the KinCon reporter technology to examine the impact of regulatory protein interactions on LKB1 kinase tumor suppressor functions. Third, we explore the conformational dynamics of RIP kinases in response to TNF pathway activation and small molecule interactions. Finally, we show that CDK4/6 interactions with regulatory proteins alter conformations which remain unaffected in the presence of clinically applied inhibitors. Apart from its predictive value, the KinCon technology helps to identify cellular factors that impact drug efficacies. The understanding of the structural dynamics of full-length protein kinases when interacting with small molecule inhibitors or regulatory proteins is crucial for designing more effective therapeutic strategies.

Impact of protein and small molecule interactions on kinase conformations

Protein kinases act as central molecular switches in the control of cellular functions. Alterations in the regulation and function of protein kinases may provoke diseases including cancer. In this study we investigate the conformational states of such disease-associated kinases using the high sensitivity of the kinase conformation (KinCon) reporter system. We first track BRAF kinase activity conformational changes upon melanoma drug binding. Second, we also use the KinCon reporter technology to examine the impact of regulatory protein interactions on LKB1 kinase tumor suppressor functions. Third, we explore the conformational dynamics of RIP kinases in response to TNF pathway activation and small molecule interactions. Finally, we show that CDK4/6 interactions with regulatory proteins alter conformations which remain unaffected in the presence of clinically applied inhibitors. Apart from its predictive value, the KinCon technology helps to identify cellular factors that impact drug efficacies. The understanding of the structural dynamics of full-length protein kinases when interacting with small molecule inhibitors or regulatory proteins is crucial for designing more effective therapeutic strategies.

The Influence of Acetone on the Kinetics of Water Electrolysis Examined at Polycrystalline Pt Electrode in Alkaline Solution

This study investigated the impact of acetone on the electrochemical behavior of polycrystalline platinum electrodes in 0.1 M NaOH solution, with respect to the kinetics of hydrogen and oxygen evolution reactions (HER and OER) and indirectly to the underpotential deposition of hydrogen (UPDH). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques were employed to analyze these processes for acetone concentrations ranging from 1.0 × 10−6 to 1.0 × 10−3 M. The addition of (CH3)2C=O enhanced the catalytic efficiency of alkaline water splitting, which was believed to be a result of a significant reduction in the surface tension phenomenon (due to mutual interaction of acetone and water molecules), thus considerably facilitating hydrogen bubble detachment from the Pt electrode. Key findings in this work are described with respect to facilitation of both the HER and the OER reactions’ kinetics by the presence of acetone (also undergoing Pt electroreduction over the potential range for UPDH) in the working solution, without an electrode surface poisoning effect. The latter implies significant opportunities for traces of organic additives into alkaline electrolyte to improve the industrial alkaline water electrolysis process.

Reaction mechanism of CO2 on the surface δ-Pu(1 0 0):a DFT study

This investigation elucidates the adsorptive and dissociative interactions of CO2 and CO molecules with the δ-Pu (100) surface, utilizing state-of-the-art first-principles calculations. The study unearths that the hollow site epitomizes the most favorable adsorption locus for both CO2 and CO. Within the paramount adsorption configuration, there prevails a propensity for both species to partake in dissociative adsorption, characterized by CO2 cleaving into an O atom and a concomitant CO moiety, whereas CO disintegrates into discrete C and O atoms. The dissociation energy barriers conducive to such configurations are computed to be 3.0568 eV for CO2 and 5.1667 eV for CO. A thorough analysis of electronic charges and density of states intimates a transfer of electrons from the Plutonium surface atoms to the carbonaceous adsorbates during dissociation. Post dissociation of the C-O bond, the 6d orbitals of Plutonium engage in electronic hybridization with the 2p orbitals of Carbon, culminating in the constitution of ionic bonding.

Plenty of molecule structures and interaction solutions in liquid–gas bubble dynamical system

Plenty of molecule structures and interaction solutions in liquid–gas bubble dynamical system

Effect of the Nature of Nitrogen-Containing Organic Base on Destruction of Octa(4-tert-butylphenyl)tetrapyrazinoporphyrazine

The properties of octa(4-tert-butylphenyl)tetrapyrazinoporphyrazine in 2-methylpyridine were studied. During the acid-base interaction of molecules, a kinetically stable complex was formed with proton transfer. The addition of morpholine, piperidine, n-butylamine, and diethylamine to 2-methylpyridine led to the destruction of this complex, unlike the addition of tert-butylamine and triethylamine. The influence of the proton-accepting ability and spatial structure of the nitrogen-containing base, as well as the basicity of the medium, on the process of the tetrapyrazinoporphyrazine macrocycle decomposition was considered, and a destruction scheme was proposed.

Investigation of pyridine-bearing thiazolidinone derivatives as promising inhibitors of thymidine phosphorylase and α-glucosidase: Theoretical and computational approaches to develop multitarget drugs

The present study reports the new pyridine-containing analogs bearing thiazolidinone moieties (1–15), which were synthesized and their biological activity was assessed against thymidine phosphorylase and α-glucosidase enzymes. Some of the analogues with the same basic structure but different substituents were discovered to have strong potential against the targeted enzymes, while other analogues were found to have medium to moderate activity in the tested series. These analogues showed a varied range of inhibition in the case of thymidine phosphorylase, 1 (IC50 = 5.70 ± 0.20 µM), 5 (IC50 = 4.50 ± 0.50 µM), 6 (IC50 = 4.60 ± 0.20 µM) and 12 (IC50 = 6.30 ± 0.20 µM), compared with standard 7-Deazaxanthine, 7DX (IC50 = 32.68 ± 1.20 µM). Similarly, excellent inhibitory profiles were also shown by these analogues in the case of alpha-glucosidase inhibition activity, 1 (IC50 =1.80 ± 0.20 µM), 5 (IC50 =1.40 ± 0.10 µM) 6 (IC50 =2.50 ± 0.60 µM) and 12 (IC50 =3.10 ± 0.30 µM) when compared with standard drug acarbose (IC50 = 3.30 ± 1.30 µM). These analogues were also subjected to molecular docking studies against using the PDB id of 1UOU for thymidine phosphorylase (PDB Id: 1UOU) and alpha-glucosidase ((PDB Id: 3w37), for exploration of binding interactions of molecules with active site of the enzymes. ADME studies also predicted the drug-like properties of these analogues.

Doxorubicin as a Drug Repurposing for Disruption of α-Chymotrypsinogen-A Aggregates.

Protein conformation is affected by interaction of several small molecules resulting either stabilization or disruption depending on the nature of the molecules. In our earlier communication, Hg2+ was known to disrupt the native structure of α-Cgn A leading to aggregation (Ansari, N.K., Rais, A. & Naeem, A. Methotrexate for Drug Repurposing as an Anti-Aggregatory Agent to Mercuric Treated α-Chymotrypsinogen-A. Protein J (2024). https://doi.org/10.1007/s10930-024-10187-z ). Accumulation of β-rich aggregates in the living system is found to be linked with copious number of disorders. Here, we have investigated the effect of varying concentration of doxorubicin (DOX) i.e. 0-100 µM on the preformed aggregates of α-Cgn A upon incubation with 120 µM Hg2+. The decrease in the intrinsic fluorescence and enzyme activity with respect to increase in the Hg2+ concentration substantiate the formation of aggregates. The DOX showed the dose dependent decrease in the ThT fluorescence, turbidity and RLS measurements endorsing the dissolution of aggregates which were consistent with red shift in ANS, confirming the breakdown of aggregates. The α-Cgn A has 30% α-helical content which decreases to 3% in presence of Hg2+. DOX increased the α-helicity to 28% confirming its anti-aggregatory potential. The SEM validates the formation of aggregates with Hg2+ and their dissolution upon incubation with the DOX. Hemolysis assay checked the cytotoxicity of α-Cgn A aggregates. Docking revealed that the DOX interacted Lys203, Cys201, Cys136, Ser159, Leu10, Trp207, Val137 and Thr134 of α-Cgn A through hydrophobic interactions and Gly133, Thr135 and Lys202 forms hydrogen bonds.

Infrared Reflection-Absorption Spectroscopy (IRRAS) applied to oxides: Ceria as a case study

Infrared Reflection-Absorption Spectroscopy (IRRAS), a pivotal tool in the study of the surface chemistry of metals, has recently also gained substantial impact for oxide surfaces, despite the inherent challenges originating from their dielectric properties. This review focuses on the application of IRRAS to ceria (CeO2), a metal oxide for which a significant amount of experimental data exists. We elaborate on the differences in optical properties between metals and metal oxides, which result in lower intensity of adsorbate vibrational bands by approximately two orders of magnitude and polarization-dependent shifts of vibrational frequencies. We examine how the surface selection rule, governing IR spectroscopy of adsorbates on metals, contrasts sharply with the behavior of dielectrics where both positive and negative vibrational bands can occur, and how IRRAS can capture vibrations with transition dipole moments oriented parallel to the surface—a capability not feasible on metallic surfaces. Finally, this paper explores the broader implications of these findings for enhancing our understanding of molecule interactions on oxide surfaces, and for using IR spectroscopy for operando studies under technologically relevant conditions.

Functionalizing Surfaces by Physical Vapor Deposition To Measure the Degree of Nanoscale Contact Using FRET.

Adhesion between solid materials is caused by intermolecular forces that only take place if the adhering surfaces are at nanoscale contact (NSC) (i.e., 0.1-0.4 nm. To study adhesion, NSC can be evaluated with Förster Resonance Energy Transfer (FRET). FRET uses the interaction of compatible fluorescence molecules to measure the nanometer distance between bonded surfaces. For this, each surface is labeled with one fluorescence dye, named the Donor or Acceptor. If these molecules are in NSC, a nonradiative Donor-Acceptor energy transfer will occur and can be detected using FRET spectroscopy. Here, for the first time, we introduce an innovative concept of a FRET-based NSC measurement employing dye-nanolayer films prepared by a physical vapor deposition (PVD). The dye nanolayers were prepared by PVD from the vaporization of the Donor and Acceptor molecules separately. The selected molecules, 7-Amino-4-methyl-cumarin (C120) and 5(6)-Carboxy-2',7'-dichlor-fluorescein (CDCF), present high quantum yields (QY, QYD = 0.91 and QYA = 0.64) and a low FRET distance range of 0.6-2.2 nm, adequate for the study of NSC. The produced dye-nanolayer films exhibit a uniform dye distribution (verified by atomic force microscopy) and suitable fluorescence intensities. To validate the NSC measurements, FRET spectroscopy experiments were performed with bonded dye-nanolayer films prepared under different loads (from 1.5 to 140 bar), thus creating different degrees of NSC. The results show an increase in FRET intensity (R 2 = 0.95) with the respective adhesion energy between the films, which is directly related to the degree of NSC. Hence, this work establishes FRET as an experimental technique for the measurement of NSC, and its relation to surface adhesion. Additionally, thanks to the FRET dye-nanolayer approach, the method can be employed on arbitrary surfaces. Essentially, any sufficiently transparent substrate can be functionalized with FRET compatible dyes to evaluate NSC, which represents a breakthrough in contact mechanics investigations of soft and hard solid materials.

Phytochemical and biological studies on rare and endangered plants endemic to China. Part XXXVI. Tsugaforrestiacids A–O: Structurally diverse C-18 carboxylated diterpenoids from the twigs and needles of the ‘vulnerable’ conifer Tsuga forrestii and their inhibitory effects on ATP-citrate lyase

An extensive phytochemical investigation on the EtOAc-soluble fraction of the 90% MeOH extract from the twigs and needles of the ‘vulnerable’ Chinese endemic conifer Tsuga forrestii (Forrest's hemlock) led to the isolation and characterization of 50 structurally diverse diterpenoids, including 15 unreported C-18 carboxylated ones (tsugaforrestiacids A−O, 1−15, resp.). Among them, compounds 1−7 are abieten-18-oic acids, compound 8 is an abieten-18-succinate, and compounds 10−12 are podocarpen-18-oic acids, whereas compounds 13−15 are pimarane-type, isopimarane-type, and totarane-type diterpenoid acids, respectively. Their structures and absolute configurations were determined by a combination of spectroscopic methods, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism (ECD) data, and single crystal X-ray diffraction analyses. All the isolates were evaluated for their inhibitory activities against the ATP-citrate lyase (ACL), a key enzyme in cellular metabolism. Tsugaforrestiacids E (5) and H (8) were found to have significant inhibitory effects against ACL, with IC50 values of 5.3 and 6.2 μM, respectively. The interactions of the bioactive molecules with the ACL enzyme were examined by molecular docking studies. The isolated diterpenoids also provide chemotaxonomic evidence to support the delimitation of Tsuga from its closest sister group (Nothotsuga). The above findings highlight the importance of protecting plant species with unique and diverse secondary metabolites, which may be potential sources of new therapeutic agents for the treating ACL-associated diseases.

Long-Acting Antibacterial Hydrogels Constructed by Interface-Induced Directional Assembly.

Self-assembled supermolecular hydrogels of therapeutic agents without structural modification are of great significance in biomedical applications. Nevertheless, the complex conformations and elusive interactions of therapeutic molecules limit the controlled assembly of hydrogels. Molecules at the interface might have different arrangements and assemblies compared to those in bulk aqueous solution, which could potentially alter the selectivity of supramolecular polymorphs. However, this effect is still not well understood. Here, we demonstrate the interface-induced self-assembly of fibers for hydrogels, which is distinct from the spherical aggregates in the bulk aqueous solution, using cephradine (CEP) as a model compound. This phenomenon is caused by the packing of anisotropic molecules at the interface, and it can be applied to control the supramolecular polymorphism for the direct self-assembly of hydrogels of therapeutic agents. The interface-induced hydrogel exhibits a high degree of adjustable release and a long-acting bactericidal effect.

Study of CO2 Adsorption Properties on the SrTiO3(001) Surface with Ambient Pressure XPS.

The adsorption properties of CO2 on the SrTiO3(001) surface were investigated using ambient pressure X-ray photoelectron spectroscopy under elevated pressure and temperature conditions. On the Nb-doped TiO2-enriched (1 × 1) SrTiO3 surface, CO2 adsorption, i.e., the formation of CO3 surface species, occurs first at the oxygen lattice site under 10-6 mbar CO2 at room temperature. The interaction of CO2 molecules with oxygen vacancies begins when the CO2 pressure increases to 0.25 mbar. The adsorbed CO3 species on the Nb-doped SrTiO3 surface increases continuously as the pressure increases but starts to leave the surface as the surface temperature increases, which occurs at approximately 373 K on the defect-free surface. On the undoped TiO2-enriched (1 × 1) SrTiO3 surface, CO2 adsorption also occurs first at the lattice oxygen sites. Both the doped and undoped SrTiO3 surfaces exhibit an enhancement of the CO3 species with the presence of oxygen vacancies, thus indicating the important role of oxygen vacancies in CO2 dissociation. When OH species are removed from the undoped SrTiO3 surface, the CO3 species begin to form under 10-6 mbar at 573 K, thus indicating the critical role of OH in preventing CO2 adsorption. The observed CO2 adsorption properties of the various SrTiO3 surfaces provide valuable information for designing SrTiO3-based CO2 catalysts.

Phase transition in polymer hydrogels investigated by swelling, DSC, FTIR and NMR

AbstractThe swelling and thermal behavior of single (SN) and double network (DN) hydrogels containing polyacrylamide (PAAm) and temperature sensitive poly(N, N-diethylacrylamide) (PNNDEAAm) were investigated by gravimetry and differential scanning calorimetry (DSC). Changes of the hydration of carbonyl groups and mobility of polymer network chains in the hydrogels with temperature were studied by Fourier-transformed infrared and proton nuclear magnetic resonance (1H NMR) spectroscopy. The enthalpy of dissociation of the hydrophobic interaction, minimum and maximum numbers of water molecules per monomer unit in PNNDEAAm SN hydrogel involved in the hydrophobic hydration were determined by DSC. The volume phase transition accompanied by expulsion/uptake of water and heat absorption/release in heating/cooling was exhibited by all DN hydrogels containing PNNDEAAm. In these hydrogels, above the phase transition temperature, the population of hydrated carbonyls is enriched with the free and single hydrated ones in the same way as in the aqueous solution of linear PNNDEAAm and mobility of the PNNDEAAm chains is strongly reduced. Presence of the PAAm network does not influence the phase transition temperature but strongly reduces the enthalpy of the phase transition, promotes higher degrees of hydration of carbonyls, and increases mobility of the PNNDEAAm chains in the mixed hydrogels above the phase transition temperature.

NUSAP1 Promotes Immunity and Apoptosis by the SHCBP1/JAK2/STAT3 Phosphorylation Pathway to Induce Dendritic Cell Generation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with high morbidity and mortality rates. The aims of this study were to investigate the immune-promoting action of nucleolar and spindle-associated protein 1 (NUSAP1) and identify an immunotherapy target for HCC. The Cancer Genome Atlas (TCGA) was used to analyze interaction molecules and immune correlation. The interaction between NUSAP1 and SHC binding and spindle associated 1 (SHCBP1) was examined. The role of the SHCBP1/Janus kinase 2/signal transducer and activator of transcription 3 (SHCBP1/JAK2/STAT3) pathway in this process was explored. After co-culture with HCC cell lines, the differentiation of peripheral blood mononuclear cells (PBMCs) into dendritic cells (DC) was evaluated by measuring the expression of surface factors CD1a and CD86. Pathological tissues from 50 patients with HCC were collected to validate the results of cell experiments. The expression levels of CD1a and CD86 in tissues were also determined. The results show that NUSAP1 interacted with SHCBP1 and was positively correlated with DC. In HCC cell lines, an interaction was observed between NUSAP1 and SHCBP1. It was verified that NUSAP1 inhibited the JAK2/STAT3 phosphorylation pathway by blocking SHCBP1. After co-culture, the levels of CD1a and CD86 in PBMC were elevated. In the clinical specimens, CD1a and CD86 expression levels were significantly higher in the high-NUSAP1 group versus the low-NUSAP1 group. In Summary, NUSAP1 enhanced immunity by inhibiting the SHCBP1/JAK2/STAT3 phosphorylation pathway and promoted DC generation and HCC apoptosis. NUSAP1 may be a target of immunotherapy for HCC.

Editorial: Interaction and dynamics of biological molecules

Editorial: Interaction and dynamics of biological molecules

Dataset for quantum-mechanical exploration of conformers and solvent effects in large drug-like molecules

We here introduce the Aquamarine (AQM) dataset, an extensive quantum-mechanical (QM) dataset that contains the structural and electronic information of 59,783 low-and high-energy conformers of 1,653 molecules with a total number of atoms ranging from 2 to 92 (mean: 50.9), and containing up to 54 (mean: 28.2) non-hydrogen atoms. To gain insights into the solvent effects as well as collective dispersion interactions for drug-like molecules, we have performed QM calculations supplemented with a treatment of many-body dispersion (MBD) interactions of structures and properties in the gas phase and implicit water. Thus, AQM contains over 40 global and local physicochemical properties (including ground-state and response properties) per conformer computed at the tightly converged PBE0+MBD level of theory for gas-phase molecules, whereas PBE0+MBD with the modified Poisson-Boltzmann (MPB) model of water was used for solvated molecules. By addressing both molecule-solvent and dispersion interactions, AQM dataset can serve as a challenging benchmark for state-of-the-art machine learning methods for property modeling and de novo generation of large (solvated) molecules with pharmaceutical and biological relevance.

Store-operated calcium entry dysfunction in CRAC channelopathy: Insights from a novel STIM1 mutation

Store-operated calcium entry (SOCE) plays a crucial role in maintaining cellular calcium homeostasis. This mechanism involves proteins, such as stromal interaction molecule 1 (STIM1) and ORAI1. Mutations in the genes encoding these proteins, especially STIM1, can lead to various diseases, including CRAC channelopathies associated with severe combined immunodeficiency. Herein, we describe a novel homozygous mutation, NM_003156 c.792-3C > G, in STIM1 in a patient with a clinical profile of CRAC channelopathy, including immune system deficiencies and muscle weakness. Functional analyses revealed three distinct spliced forms in the patient cells: wild-type, exon 7 skipping, and intronic retention. Calcium influx analysis revealed impaired SOCE in the patient cells, indicating a loss of STIM1 function. We developed an antisense oligonucleotide treatment that improves STIM1 splicing and highlighted its potential as a therapeutic approach. Our findings provide insights into the complex effects of STIM1 mutations and shed light on the multifaceted clinical presentation of the patient.

Exploring the antidiabetic and anti-inflammatory potential of Lavandula officinalis essential oil: In vitro and in silico insights

Medicinal plants have been utilized for centuries in traditional medicine systems worldwide, providing a rich source of bioactive compounds with diverse biological activities. Lavandula officinalis, a member of the Lamiaceae family, has been recognized for its multifaceted pharmacological activities. In this current investigation, our primary objective was to scrutinize the in vitro inhibitory potential of L. officinalis essential oil (LOEO) against alpha-amylase and alpha-glucosidase, with the aim of understanding its antidiabetic effects. Additionally, the assay encompassed tyrosinase and lipoxygenase (LOX) to assess its anti-inflammatory attributes. Unraveling the underlying molecular mechanisms of these activities prompted an in-silico study. The purpose was to establish correlations between in-vitro observations and computational insights derived from molecular docking, which forecasts the interaction of LOEO molecules with their respective targets, alongside ADMET prediction. The Gas Chromatography-Mass Spectrometry (GC-MS) analysis allow to identify eighteen compounds, with the dominance of L−camphor (43.12 %), 1,8−cineole (34.27 %) and borneol (8.60 %) in LOEO. The antidiabetic evaluation revealed that LOEO exhibited noteworthy inhibitory activity against both α-amylase and α-glucosidase, displaying IC50 values of 3.14 ± 0.05 mg/mL and 2.07 ± 0.03 mg/mL, respectively. The subsequent in-silico study highlighted the particularly strong binding affinity of (E)-Farnesene, with a binding score of −7.4 kcal/mol for alpha-glucosidase, while Germacrene D displayed the highest affinity among the ligands (−7.9 kcal/mol) for the alpha-amylase target. Furthermore, the investigation into in vitro anti-inflammatory activity unveiled LOEO efficacy against tyrosinase (IC50 = 42.74 μg/mL) and LOX (IC50 = 11.58 ± 0.07 μg/mL). The in-silico analysis echoed these findings, indicating α-Cadinene's notable binding affinity of 6 kcal/mol with tyrosinase and α-Cedrene's binding score of −6.5 kcal/mol for LOX. Impressively, for both COX-1 and COX-2, α-Cedrene exhibited significant binding affinities of −7.6 and −7.3 kcal/mol, respectively. The convergence between the in vitro and in silico outcomes underscores the potential of LOEO and its constituent compounds as potent inhibitors targeting both diabetes and the inflammatory processes.