Phytoremediation Potential of Three Species of Macrophytes for Nitrate in Contaminated Water

Abstrac

Sulfur-Doped BiOCl with Enhanced Light Absorption and Photocatalytic Water Oxidation Activity

Photocatalysis is a powerful strategy to address energy and environmental concerns. Sulfur-doped BiOCl was prepared through a facial hydrothermal method to improve the photocatalytic performance. Experimental results and theoretical calculations demonstrated that the band structure of the sulfur-doped BiOCl was optimally regulated and the light absorption range was expanded. It showed excellent visible-light photocatalytic water oxidation properties with a rate of 141.7 μmol h−1 g−1 (almost 44 times of that of the commercial BiOCl) with Pt as co-catalyst

Molecular Modeling Study on the Allosteric Inhibition Mechanism of HIV-1 Integrase by LEDGF/p75 Binding Site Inhibitors

<div><p>HIV-1 integrase (IN) is essential for the integration of viral DNA into the host genome and an attractive therapeutic target for developing antiretroviral inhibitors. LEDGINs are a class of allosteric inhibitors targeting LEDGF/p75 binding site of HIV-1 IN. Yet, the detailed binding mode and allosteric inhibition mechanism of LEDGINs to HIV-1 IN is only partially understood, which hinders the structure-based design of more potent anti-HIV agents. A molecular modeling study combining molecular docking, molecular dynamics simulation, and binding free energy calculation were performed to investigate the interaction details of HIV-1 IN catalytic core domain (CCD) with two recently discovered LEDGINs BI-1001 and CX14442, as well as the LEDGF/p75 protein. Simulation results demonstrated the hydrophobic domain of BI-1001 and CX14442 engages one subunit of HIV-1 IN CCD dimer through hydrophobic interactions, and the hydrophilic group forms hydrogen bonds with HIV-1 IN CCD residues from other subunit. CX14442 has a larger <i>tert</i>-butyl group than the methyl of BI-1001, and forms better interactions with the highly hydrophobic binding pocket of HIV-1 IN CCD dimer interface, which can explain the stronger affinity of CX14442 than BI-1001. Analysis of the binding mode of LEDGF/p75 with HIV-1 IN CCD reveals that the LEDGF/p75 integrase binding domain residues Ile365, Asp366, Phe406 and Val408 have significant contributions to the binding of the LEDGF/p75 to HIV1-IN. Remarkably, we found that binding of BI-1001 and CX14442 to HIV-1 IN CCD induced the structural rearrangements of the 140 s loop and oration displacements of the side chains of the three conserved catalytic residues Asp64, Asp116, and Glu152 located at the active site. These results we obtained will be valuable not only for understanding the allosteric inhibition mechanism of LEDGINs but also for the rational design of allosteric inhibitors of HIV-1 IN targeting LEDGF/p75 binding site.</p></div

Deciphering the Effect of Lysine Acetylation on the Misfolding and Aggregation of Human Tau Fragment 171IPAKTPPAPK180 Using Molecular Dynamic Simulation and the Markov State Model

The formation of neurofibrillary tangles (NFT) with &beta;-sheet-rich structure caused by abnormal aggregation of misfolded microtubule-associated protein Tau is a hallmark of tauopathies, including Alzheimer&rsquo;s Disease. It has been reported that acetylation, especially K174 located in the proline-rich region, can largely promote Tau aggregation. So far, the mechanism of the abnormal acetylation of Tau that affects its misfolding and aggregation is still unclear. Therefore, revealing the effect of acetylation on Tau aggregation could help elucidate the pathogenic mechanism of tauopathies. In this study, molecular dynamics simulation combined with multiple computational analytical methods were performed to reveal the effect of K174 acetylation on the spontaneous aggregation of Tau peptide 171IPAKTPPAPK180, and the dimerization mechanism as an early stage of the spontaneous aggregation was further specifically analyzed by Markov state model (MSM) analysis. The results showed that both the actual acetylation and the mutation mimicking the acetylated state at K174 induced the aggregation of the studied Tau fragment; however, the effect of actual acetylation on the aggregation was more pronounced. In addition, acetylated K174 plays a major contributing role in forming and stabilizing the antiparallel &beta;-sheet dimer by forming several hydrogen bonds and side chain van der Waals interactions with residues I171, P172, A173 and T175 of the corresponding chain. In brief, this study uncovered the underlying mechanism of Tau peptide aggregation in response to the lysine K174 acetylation, which can deepen our understanding on the pathogenesis of tauopathies

Electrostatic potential surface of the allosteric binding pocket of HIV-1 IN CCD dimer in interaction with (A) BI-1001, (B) CX14442, and (C) LEDGF/p75.

<p>The positive charges are displayed in blue, negative charges are displayed in red, and neutral residues are displayed in white. Color intensity is proportional to the charge value. The BI-1001, CX14442 and side chain of the LEDGF/p75 key residues, whose carbon atoms are shown as green spheres and labeled as red. The residue Trp131 from monomer A of HIV-1 CCD dimer is also labeled (black).</p

Binding Thermodynamics and Dissociation Kinetics Analysis Uncover the Key Structural Motifs of Phenoxyphenol Derivatives as the Direct InhA Inhibitors and the Hotspot Residues of InhA

Given the current epidemic of multidrug-resistant tuberculosis, there is an urgent need to develop new drugs to combat drug-resistant tuberculosis. Direct inhibitors of the InhA target do not require activation and thus can overcome drug resistance caused by mutations in drug-activating enzymes. In this work, the binding thermodynamic and kinetic information of InhA to its direct inhibitors, phenoxyphenol derivatives, were explored through multiple computer-aided drug design (CADD) strategies. The results show that the van der Waals interactions were the main driving force for protein&ndash;ligand binding, among which hydrophobic residues such as Tyr158, Phe149, Met199 and Ile202 have high energy contribution. The AHRR pharmacophore model generated by multiple ligands demonstrated that phenoxyphenol derivatives inhibitors can form pi&ndash;pi stacking and hydrophobic interactions with InhA target. In addition, the order of residence time predicted by random acceleration molecular dynamics was consistent with the experimental values. The intermediate states of these inhibitors could form hydrogen bonds and van der Waals interactions with surrounding residues during dissociation. Overall, the binding and dissociation mechanisms at the atomic level obtained in this work can provide important theoretical guidance for the development of InhA direct inhibitors with higher activity and proper residence time

The LEDGF/p75 protein residues contribution to the total binding free energy of the LEDGF/p75 bound HIV-1 IN CCD complex.

<p>The LEDGF/p75 protein residues contribution to the total binding free energy of the LEDGF/p75 bound HIV-1 IN CCD complex.</p

Per-residue interaction spectrum of the residues of HIV-1 IN CCD with (A) BI-1001, (B) CX14442, and (C) LEDGF/p75 in complex with the HIV-1 IN CCD dimer from MM/GBSA free energy decomposition analysis.

<p>Per-residue interaction spectrum of the residues of HIV-1 IN CCD with (A) BI-1001, (B) CX14442, and (C) LEDGF/p75 in complex with the HIV-1 IN CCD dimer from MM/GBSA free energy decomposition analysis.</p