Molecular docking and molecular dynamics simulations revealed interaction mechanism of acetylcholinesterase with organophosphorus pesticides and their alternatives.

Organophosphate pesticides (OPs) are widely used in agricultural fields and can inhibit the activity of human acetylcholinesterase (hAChE) by covalently binding to serine at the enzyme's active site. However, the molecular recognition mechanisms beyond their covalent binding remain unclear. This study employed molecular docking along with molecular dynamics simulations (MD) to investigate four representative OPs, Phosphamidon, Monocrotophos, Dichlorvos, and Trichlorfon, as well as two potential alternatives Magnolol (MAG) and Honokiol (HON), to understand the conformational change of hAChE and its molecular recognition mechanism.

Insight into the Binding Interaction between PEDCs and hERRγ Utilizing Molecular Docking and Molecular Dynamics Simulations.

Phenolic environmental endocrine-disrupting chemicals (PEDCs) are persistent EDCs that are widely found in food packaging materials and environmental media and seriously threaten human health and ecological security. Human estrogen-related receptor γ (hERRγ) has been proposed as a mediator for the low-dose effects of many environmental PEDCs; however, the atomic-level descriptions of dynamical structural features and interactions of hERRγ and PEDCs are still unclarified. Herein, how three PEDCs, 4-(1-methylpropyl)phenol (4-sec-butylphenol), 5,6,7,8-tetrahydro-2-naphthol (tetrahydro-2-napthol), and 2,2-bis(4-hydroxy-3,5-dimethoxyphenyl)propane (BP(2,2)(Me)), interact with hERRγ to produce its estrogenic disruption effects was studied.

Molecular recognition between volatile molecules and odorant binding proteins 7 by homology modeling, molecular docking and molecular dynamics simulation.

Background: Odorant-binding proteins (OBPs) in insects are key to detection and recognition of external chemical signals associated with survival. OBP7 in Spodoptera frugiperda's larval stage (SfruOBP7) may search for host plants by sensing plant volatiles, which are important sources of pest attractants and repellents. However, the atomic-level basis of binding modes remains elusive.

2D MoB MBene: An Efficient Co-Catalyst for Photocatalytic Hydrogen Production under Visible Light.

Highly active and low-cost co-catalysts have a positive effect on the enhancement of solar H production. Here, we employ two-dimensional (2D) MBene as a noble-metal-free co-catalyst to boost semiconductor for photocatalytic H production. MoB MBene is a 2D nanoboride, which is directly made from MoAlB by a facile hydrothermal etching and manual scraping off process.

Molecular docking and molecular dynamics simulation decoding molecular mechanism of EDCs binding to hERRγ.

Context: Human estrogen-related receptor γ (hERRγ) is a key protein involved in various endocrines and metabolic signaling. Numerous environmental endocrine-disrupting chemicals (EDCs) can impact related physiological activities through receptor signaling pathways. Focused on hERRγ with 4-isopropylphenol, bisphenol-F (BPF), and BP(2,2)(Un) complexes, we executed molecular docking and multiple molecular dynamics (MD) simulations along with molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) and solvation interaction energy (SIE) calculation to study the detailed dynamical structural characteristics and interactions between them.

Molecular basis of RNA recognition by TBP of HIV-1 from multiple molecular dynamics simulations and energy predictions.

The frequent outbreaks of the AIDS (Acquired Immune Deficiency Syndrome) pandemic and the limited availability of anti-Human Immunodeficiency Virus (HIV) drugs highlight the urgent need to develop new antiviral drugs. A detailed understanding of the interactions between TAR-Binding Proteins (TBP) and RNA will facilitate the discovery of new anti-AIDS drugs. In order to characterize and explore the key interactions between RNA and TBP, we focused on the wild type (WT) and three mutant TBPs (TBP6.

Molecular basis of ssDNA recognition by RBM45 protein of neurodegenerative disease from multiple molecular dynamics simulations and energy predictions.

Neurodegenerative diseases (NDD) are a group of cognitive and behavioral disorders characterized by progressive loss of neuronal structure and function. As the population ages, the incidence is getting higher and higher, but there is currently no effective treatment. The details of RNA/DNA recognition by the RNA-binding protein RBM45 closely related to neurodegenerative diseases through its two tandem RNA-recognition domains at its N-terminus have important implications for structure-based drug discovery against degenerative diseases.

Structural and energetic basis of interaction between human estrogen-related receptor γ and environmental endocrine disruptors from multiple molecular dynamics simulations and free energy predictions.

Environmental endocrine disruptors (EEDs), a class of molecules that are widespread in our environment, may adversely affect the endocrine system. Exploring the interactions between these compounds and their potential targets is important for assessing their role in the organism. Focused on the human estrogen-related receptor γ (hERRγ) with BPA, BPB, HPTE, BPE, BP(2,2)(Et), and BP(2,2)(MeO) complexes, respectively, we groped for the mechanisms of conformational changes and interactions of hERRγ when binding to these six EEDs by combining multiple molecular dynamics (MD) simulations with energy prediction (MM-PBSA and solvated interaction energy (SIE)).

Multiple Molecular Dynamics Simulations and Energy Analysis Unravel the Dynamic Properties and Binding Mechanism of Mutants HIV-1 Protease with DRV and CA-p2.

PR, a variant of human immunodeficiency virus type I protease (HIV-1 PR), has 17 mutated residues showing high levels of multidrug resistance. To describe the effects of these mutated residues on the dynamic properties and the binding mechanism of PR with substrate and inhibitor, focused on six systems (two complexes of WT PR and PR with inhibitor Darunavir (DRV), two complexes of WT PR and PR with substrate analogue CA-p2, two unligand WT PR and PR), we performed multiple molecular dynamics (MD) simulations combined with MM-PBSA and solvated interaction energy (SIE) methods. For both the unligand PRs and ligand-PR complexes, the results from simulations revealed 17 mutated residues alter the flap-flap distance, the distance from flap regions to catalytic sites, and the curling degree of the flap tips.

Multiple Molecular Dynamics Simulations and Free-Energy Predictions Uncover the Susceptibility of Variants of HIV-1 Protease against Inhibitors Darunavir and KNI-1657.

HIV-1 protease (PR) is considered to be the main targets of anti-AIDS drug design because of its role in the proteolytic processing of viral polyproteins. However, the emergence of drug-resistant HIV has become a major problem in the therapy of HIV-1-infected patients. Focused on the complexes of wild type (WT) PR and two mutant PRs (V32I/L33F/I54M/V82I and V32I/L33F/I54M/I84 V) with inhibitors Darunavir (DRV) and KNI-1657 (KNI), respectively, we have conducted research on the conformational dynamics and the resistance mechanism caused by residue mutations through multiple molecular dynamics (MD) simulations combined with an energy (MM-PBSA and solvated interaction energy (SIE)) prediction.

Electrochemical Enabled Cascade Phosphorylation of N-H/O-H/S-H Bonds with P-H Compounds: An Efficient Access to P(O)-X Bonds.

An electrochemical three component cascade phosphorylation reaction of various heteroatoms-containing nucleophiles including carbazoles, indoles, phenols, alcohols, and thiols with Ph PH has been established. Electricity is used as the "traceless" oxidant and water and air are utilized as the "green" oxygen source. All kinds of structurally diverse organophosphorus compounds with P(O)-N/P(O)-O/P(O)-S bonds are assembled in moderate to excellent yields (three categories of phosphorylation products, 50 examples, up to 97 % yield).

Multiple Molecular Dynamics Simulations of the Inhibitor GRL-02031 Complex with Wild Type and Mutant HIV-1 Protease Reveal the Binding and Drug-Resistance Mechanism.

Human immunodeficiency virus type 1 (HIV-1) protease is regarded as a fascinating target for drug development against HIV infection. However, mutations causing drug resistance severely limit the efficiency of the recently marketed drugs in the treatment of HIV replication. To elucidate the binding mechanism of HIV-1 protease with promising inhibitor GRL-02031 and further to probe the resistance mechanism associated with mutations (I47V, L76V, V82A, and N88D) to the inhibitor, we applied multiple molecular dynamics (MMD) simulations along with energy analysis by the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and solvated interaction energy (SIE) methodology on specific HIV-1 protease with GRL-0231 complexes.

Electrochemical Oxidative Dehydrogenative Phosphorylation of -Heterocycles with P(O)-H Compounds in Imidazolium-Based Ionic Liquid.

We report a direct and green electrochemical oxidative cross-dehydrogenative coupling reaction of -heterocycles with hydrogen phosphoryl compounds under external oxidant-free conditions. Various phosphorylation products of substituted carbazoles and indoles are assembled in modest to excellent yields. A hydrogen release process is preliminarily demonstrated and H is the sole byproduct.

Revealing the binding and drug resistance mechanism of amprenavir, indinavir, ritonavir, and nelfinavir complexed with HIV-1 protease due to double mutations G48T/L89M by molecular dynamics simulations and free energy analyses.

Infection by human immunodeficiency virus type 1 (HIV-1) not only destroys the immune system bringing about acquired immune deficiency syndrome (AIDS), but also induces serious neurological diseases including behavioral abnormalities, motor dysfunction, toxoplasmosis, and HIV-1 associated dementia. The emergence of HIV-1 multidrug-resistant mutants has become a major problem in the therapy of patients with HIV-1 infection. Focusing on the wild type (WT) and G48T/L89M mutated forms of HIV-1 protease (HIV-1 PR) in complex with amprenavir (APV), indinavir (IDV), ritonavir (RTV), and nelfinavir (NFV), we have investigated the conformational dynamics and the resistance mechanism due to the G48T/L89M mutations by conducting a series of molecular dynamics (MD) simulations and free energy (MM-PBSA and solvated interaction energy (SIE)) analyses.

CCL18 promotes the invasion and metastasis of breast cancer through Annexin A2.

Chemokine (C‑C motif) ligand 18 (CCL18) is derived from breast tumor‑associated macrophages (TAMs), which are primarily a macrophage subpopulation with an M2 phenotype. CCL18 binds to its receptor, PYK2 N‑terminal domain interacting receptor 1 (Nir1), and promotes tumor progression and metastasis by inducing epithelial‑mesenchymal transition (EMT) via the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer cells. Recent research shows that Annexin A2 (AnxA2) plays a significant role in the invasion, metastasis, angiogenesis, proliferation, F‑actin polymerization and multidrug resistance to chemotherapy of breast cancer.

Influence of the R823W mutation on the interaction of the ANKS6-ANKS3: insights from molecular dynamics simulation and free energy analysis.

The sterile alpha motif (SAM) domain of the protein ANKS6, a protein-protein interaction domain, is responsible for autosomal dominant polycystic kidney disease. Although the disease is the result of the R823W point mutation in the SAM domain of the protein ANKS6, the molecular details are still unclear. We applied molecular dynamics simulations, the principal component analysis, and the molecular mechanics Poisson-Boltzmann surface area binding free energy calculation to explore the structural and dynamic effects of the R823W point mutation on the complex ANKS6-ANKS3 (PDB ID: 4NL9) in comparison to the wild proteins.

Thermal stability and unfolding pathways of hyperthermophilic and mesophilic periplasmic binding proteins studied by molecular dynamics simulation.

The ribose binding protein (RBP), a sugar-binding periplasmic protein, is involved in the transport and signaling processes in both prokaryotes and eukaryotes. Although several cellular and structural studies have been reported, a description of the thermostability of RBP at the molecular level remains elusive. Focused on the hyperthermophilic Thermoytoga maritima RBP (tmRBP) and mesophilic Escherichia coli homolog (ecRBP), we applied molecular dynamics simulations at four different temperatures (300, 380, 450, and 500 K) to obtain a deeper insight into the structural features responsible for the reduced thermostability of the ecRBP.