Improving the Computational Efficiency of the Adaptive Biasing Force Sampling by Leveraging the Telescopic-Solvation Scheme.

The number of solvent molecules present in the system during molecular dynamics is the balancing act between the need to remove the boundary effects present in the system and the computational cost. Application of the telescopic-solvation box scheme during the estimation of the potential of mean force (PMF) can be advantageous in situations where the contribution of solvent far from the site of interest toward the whole PMF is negligible, as previously demonstrated in the case of adaptive steered molecular dynamics and umbrella sampling. This work explores the application of the telescopic-solvation box scheme during enhanced sampling by the stratified adaptive biasing force (ABF) family of methods, including ABF, extended ABF, well-tempered-metadynamics extended ABF, and multiwalker extended ABF.

Physicochemical Analysis of Cu(II)-Driven Electrochemical CO Reduction and its Competition with Proton Reduction.

The reduction of CO has become a key role in reducing greenhouse gas emissions in efforts to search for long-term responses to climate change. We report a couple of CO-reducing molecular catalysts based on earth-abundant copper complexes. These are [Cu(DPA)(PyNAP)] (1) and [Cu(DPA)(PyQl)] (2) (where, DPA=pyridine-2,6-dicarboxylate, PyNAP=2-(pyridin-2-yl)-1,8-naphthyridine, and PyQl=2-(pyridin-2-yl)quinoline).

Decoding Inhibitor Egression from Wild-Type and G2019S Mutant LRRK2 Kinase: Insights into Unbinding Mechanisms for Precision Drug Design in Parkinson's Disease.

Leucine-rich repeat kinase 2 (LRRK2) remains a viable target for drug development since the discovery of the association of its mutations with Parkinson's disease (PD). G2019S (in the kinase domain) is the most common mutation for LRRK2-based PD. Though various types of inhibitors have been developed for the kinase domain to reduce the effect of the mutation, understanding the working of these inhibitors at the molecular level is still ongoing.

Elucidating Daptomycin's Antibacterial Efficacy: Insights into the Tripartite Complex with Lipid II and Phospholipids in Bacterial Septum Membrane.

This study elucidated the mechanism of formation of a tripartite complex containing daptomycin (Dap), lipid II, and phospholipid phosphatidylglycerol in the bacterial septum membrane, which was previously reported as the cause of the antibacterial action of Dap against gram-positive bacteria via molecular dynamics and enhanced sampling methods. Others have suggested that this transient complex ushers in the inhibition of cell wall synthesis by obstructing the downstream polymerization and cross-linking processes involving lipid II, which is absent in the presence of cardiolipin lipid in the membrane. In this work, we observed that the complex was stabilized by Ca-mediated electrostatic interactions between Dap and lipid head groups, hydrophobic interaction, hydrogen bonds, and salt bridges between the lipopeptide and lipids and was associated with Dap concentration-dependent membrane depolarization, thinning of the bilayer, and increased lipid tail disorder.

Mononuclear organogermanium(IV) catalysts for a [3 + 2] cycloaddition reaction.

Three mononuclear Ge(IV) compounds, [(CH)Ge(CHNO)] (1), [(CH)Ge(CHNO)] (2), and [(CH)Ge(CHNO)] (3), have been synthesized by the reaction of pro-ligands H2L1 (CHNO), H2L2 (CHNO), and H2L3 (CHNO) with (CH)GeCl in the presence of triethylamine. All compounds were characterized by FT-IR spectroscopy and NMR spectroscopy. Single crystal X-ray diffraction analysis shows that the germanium(IV) atom exhibits a five-coordinated geometry in compounds 1 and 2.

Formate dehydrogenase activity by a Cu(II)-based molecular catalyst and deciphering the mechanism using DFT studies.

Due to the requirement to establish renewable energy sources, formic acid (FA), one of the most probable liquid organic hydrogen carriers (LOHCs), has received great attention. Catalytic formic acid dehydrogenation in an effective and environmentally friendly manner is still a challenge. The N3Q3 ligand (N3Q3 = ,-bis(quinolin-8-ylmethyl)quinolin-8-amine) and the square pyramidal [Cu(N3Q3)Cl]Cl complex have been synthesised in this work and characterised using several techniques, such as NMR spectroscopy, mass spectrometry, EPR spectroscopy, cyclic voltammetry, X-ray diffraction and DFT calculations.

Enhanced Uptake of Anticancer C6-Pep Dimer in a Model Membrane Caused by Differential p in Acidic Microenvironment.

Acidic tumor microenvironment (TME) presents a challenge for the action of antitumor drugs by acting as an additional barrier for the passive crossing of the cell membrane by chemotherapic agents playing a critical role in the proliferation of tumor cells. Anticancer lipopeptide C6-Pep dimer containing the leucine zipper motif shows an increased uptake into the model tumor membrane in TME, and application of external heat might lead to the uncoiling of the zipper, which could result in cell lysis. This work investigated the cause of this increased uptake of C6-Pep dimer into the bilayer model in TME.

Telescoping-Solvation-Box Protocol-Based Umbrella Sampling Method for Potential Mean Force Estimation.

Previously, it was shown that the telescoping box scheme, in combination with adaptive steered molecule dynamics (ASMD), can be used to estimate the potential of mean force (PMF) with a decrease in computational cost associated with large solvation boxes. Since ASMD reduces to umbrella sampling (US) in the limit of infinitely slow pulling velocity, a hypothesis was made that the telescoping box scheme can be extended to include the US method. The hypothesis was tested using the unfolding pathway of a polyalanine peptide in a water box and translocation of α-tocopherol through the human membrane.

Photoresponsive transformation from spherical to nanotubular assemblies: anticancer drug delivery using macrocyclic cationic gemini amphiphiles.

We developed NIR-light-responsive macrocyclic cationic gemini amphiphiles, one of which displayed various favorable properties of lipids. The NIR-light-mediated cleavage of the strained dioxacycloundecine ring led to the conversion of the spherical to a nanotubular self-assembly in the aqueous medium. This photo-mediated transformation from the spherical to nanotubular self-assembly resulted in the release of encapsulated hydrophobic anticancer drug molecule doxorubicin (Dox) in a controlled manner.