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In silico identification of Aloe-derived anthraquinones as potential PTP1B inhibitors: Docking and structural dynamics insights

2026-10-06T10:51:57Z

Title: In silico identification of Aloe-derived anthraquinones as potential PTP1B inhibitors: Docking and structural dynamics insights Authors: Tiwari, Sumit; Jain, Swati; Dubey, Nazneen; Saxena, Nischal; Ganeshpurkar, Aditya Abstract: Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin signaling pathway and is widely recognized as a target for treatment in type 2 diabetes. Aloe-derived anthraquinones are known for several biological activities, however their ability to inhibit PTP1B has not yet been studied in facet through computational studies. In the present study, Lipinski’s Rule of Five was used to determine if aloe anthraquinones possess drug-like properties. The study utilized AutoDock 4 to carryout molecular docking, with PTP1B (PDB ID: 2QBP) as the protein target. The study also investigated the changes in conformation via procedures such as RMSD and RMSF. The study assessed the structural integrity and adaptability of the docked complex by analyzing its radius of gyration, the extent of solvent-accessible surface area, and by comparing secondary structure. Several aglycone derivatives met Lipinski’s standards, in contrast the glycosylated compounds did not comply. The docking results suggested that aloe-emodin O-acetyl posess the notable binding affinity and established stable interactions with key catalytic residues, including Cys215, Arg221, and Tyr46. Structural analyses demonstrated that the WPD loop imparts small change in shape, less adaptability, and robust global folding when a ligand bound to it. The results altogether demonstrate that aloe- emodin O-acetyl effectively stabilizes important catalytic domains of PTP1B without altering the general arrangement of the protein. This supports its potential as a lead PTP1B inhibitor. Anthraquinones from aloe are promising leads for the development of new antidiabetic drugs. Page(s): 1125-1134

Lactate dehydrogenase: Lactate oxidation and role of ROS

2026-10-06T10:47:28Z

Title: Lactate dehydrogenase: Lactate oxidation and role of ROS Authors: Shaik, Nadiya; Andrew Gideon, Daniel; Parashar, Abhinav Abstract: Lactate dehydrogenase is a well-studied nonspecific biomarker with profound implications in diseases like cancer. In vitro investigations into the mechanism of lactate dehydrogenase action described herein are based on our group’s earlier reported thermodynamic calculations. While the reverse (pyruvate to lactate) reaction is thermodynamically favourable, the forward (lactate to pyruvate) reaction is unfavourable at physiological conditions. NADH consumption (lactate formation) rates were high, in the range of 2000-3000 M-1 s-1 contrary to the NADH formation (pyruvate formation) rates that were low (50 to < 300 M-1 s-1) under classical reaction conditions. Interestingly, the lactate to pyruvate reactions driven with ROS (peroxide, hydroxyl radical or superoxide) alone demonstrated strikingly high reaction rates (~ 700-2500 M-1 s-1). However, inclusion of lactate dehydrogenase into such reactions rapidly lowered the NADH formation rates. GC-MS and FT-IR results supported the superoxide-assisted oxidation of lactate to pyruvate in KO2 containing reaction mixtures. DFT analysis further demonstrated the strong thermodynamic viability of ROS mediated oxidation of lactate. Comprehensively, the findings suggest an alternate route of lactate oxidation, i.e., ROS mediated catalysis of lactate to pyruvate. The findings support the murburn concept because the observed ROS-dependent lactate oxidation is consistent with a central prediction of the murburn framework. Page(s): 1135-1144

Computational screening of putative small-molecule binders of Mycobacterium tuberculosis Pup using pharmacophore modelling, molecular docking and molecular dynamics simulation

2026-10-06T10:36:54Z

Title: Computational screening of putative small-molecule binders of Mycobacterium tuberculosis Pup using pharmacophore modelling, molecular docking and molecular dynamics simulation Authors: Gautambhai Chaudhari, Megha; Rajan Maniamma, Nivya; Bhimabhai Bhutiya, Krishna; Ratna Prabha, Chivukula; Joy, Amitha Abstract: The proteasome has recently gained attention as a potential drug target for tuberculosis (TB). Proteasome inhibitors like Bortezomib and Carfilzomib have demonstrated significant anti-TB activity in various cell lines and animal models of TB infection. However, their severe side effects limit their suitability as therapeutic agents against Mycobacterium tuberculosis. This highlights the need to develop inhibitors targeting enzymes that lack human counterparts Therefore, this study aims to target another protein known as Prokaryotic ubiquitin like protein (Pup) of this proteasome pathway as there is no functional analogue of it in the humans. With this scenario, the present work focuses on the computer-aided identification of novel Pup inhibitors (PupIs) via ligand-based 3-D pharmacophore modelling. The 3D structure of M. tuberculosis Pup protein, complexed with the amino-terminal coiled coil of the M. tuberculosis proteasomal ATPase Mpa (PDB ID: 3M91), was retrieved, and the B chain was extracted for further analysis. A dataset of known proteasome inhibitors from CHEMBL was screened through molecular docking. Two small molecules, Mol 14 and Mol 15, with binding energies of -6.3 kcal/mol and -7.3 kcal/mol, were identified and used to construct pharmacophore queries. These queries were validated and screened against external databases to identify potential hits. Further docking studies, pharmacokinetic predictions, toxicity assessments, and molecular dynamics (MD) simulations were conducted. Three promising inhibitors—Mol 006, Mol 265, and Mol 280—demonstrated strong binding affinities (-6.5 to -5.7 kcal/mol). MD simulations validated the stability of Mol 280 (−6.5 kcal/mol) in complex with the B chain of 3M91, with RMSD values of 3.98 Å (protein alone) and 3.55 Å (complexed with the inhibitor Mol 280), suggesting its potential as a novel PupI. These findings support further development of Mol 280 as a therapeutic candidate against MDR-TB. Page(s): 1145-1157

In silico study on assembly of Dengue virus capsid protein with core histone proteins

2026-10-06T10:34:33Z

Title: In silico study on assembly of Dengue virus capsid protein with core histone proteins Authors: Chaudhuri, Dwaipayan; Giri, Kalyan Abstract: The Dengue virus (DENV), a member of the Flaviviridae family, is a rapidly spreading pathogen that infects millions of people every year causing severe illness. The capsid (C) protein is in charge of assembling the viral RNA into a nucleocapsid. A significant amount of capsid protein relocates to the nucleus, although viral replication takes place in the cytoplasm. DENV C interacts with the four core histones according to earlier research. Therefore, DENV C functions to bind DNA and interfere with the assembly of nucleosomes through heterodimerization with core histones. Using coarsegrained in silico assembly simulations and comprehensive MD simulations to examine the interaction between the proteins, we have elucidated on the pattern of interaction between the DENV C protein and the histone proteins. Here it was seen that the interaction strength of DENV C and histones is as follows: H3> H2B> H2A> H4 with all interactions being highly stable. Our study also identifies critical residues (majorly hydrophobic residues in the hydrophobic pocket and H4 helix) in the DENV C protein responsible for these interactions. This study opens up new possibilities for antiviral drug design by advancing our understanding of the molecular interactions between viral proteins and host cell machinery. Page(s): 1158-1168