Working group report: Collider Physics

This is summary of the activities of the working group on collider physics in the IXth Workshop on High Energy Physics Phenomenology (WHEPP-9) held at the Institute of Physics, Bhubaneswar, India in January 2006. Some of the work subsequently done on these problems by the subgroups formed during the workshop is included in this report.     

Investigations of magnetic and dielectric properties of cupric oxide nanoparticles

Cupric oxide nanoparticles of ∼8-10 nm width and 40-45 nm length self assembled as large particles ∼1-1.5 μm have been investigated, in the 10-325 K temperature range, using magnetic and dielectric measurements. In magnetic measurements a single broad peak at ∼230 K in a zero field cooled sample has been observed. Coercivity, in magnetization measurements at 10 K, suggests that the nanoparticles are core-shell type particles with an antiferromagnetic core and a ferromagnetic shell. Dielectric measurements, at various frequencies from 3.7 Hz to 949 kHz, exhibit a sharp peak at 284 K followed by weak anomalies around 213 and 230 K.     

Exploring the Structural Insights on Human Laforin Mutation K87A in Lafora Disease—A Molecular Dynamics Study

Lafora disease (LD) is an autosomal recessive, progressive form of myoclonus epilepsy which affects worldwide. LD occurs mainly in countries like southern Europe, northern Africa, South India, and in the Middle East. LD occurs with its onset mainly in teenagers and leads to decline and death within 2 to 10 years. The genes EPM2A and EPM2B are commonly involved in 90 % of LD cases. EPM2A codes for protein laforin which contains an amino terminal carbohydrate binding module (CBM) belonging to the CBM20 family and a carboxy terminal dual specificity phosphatase domain. Mutations in laforin are found to abolish glycogen binding and have been reported in wet lab methods. In order to investigate on structural insights on laforin mutation K81A, we performed molecular dynamics (MD) simulation studies for native and mutant protein. MD simulation results showed loss of stability due to mutation K87A which confirmed the structural reason for conformational changes observed in laforin. The conformational change of mutant laforin was confirmed by analysis using root mean square deviation, root mean square fluctuation, solvent accessibility surface area, radius of gyration, hydrogen bond, and principle component analysis. Our results identified that the flexibility of K87A mutated laforin structure, with replacement of acidic amino acid to aliphatic amino acid in functional CBM domain, have more impact in abolishing glycogen binding that favors LD.     

Structural Insights on Mycobacterium tuberculosis Thiazole Synthase—A Molecular Dynamics/Docking Approach

Tuberculosis (TB), an epidemic disease, affects the world with death rate of two million people every year. The bacterium Mycobacterium tuberculosis was found to be a more potent and disease-prolonged bacterium among the world due to multi-drug resistance. Emergence of new drug targets is needed to overcome the bacterial resistance that leads to control epidemic tuberculosis. The pathway thiamine biosynthesis was targeting M. tuberculosis due to its role in intracellular growth of the bacterium. The screening of enzymes involved in thiamin biosynthesis showed novel target thiazole synthase (ThiG) involved in catalysis of rearrangement of 1-deoxy-d-xylulose 5-phosphate (DXP) to produce the thiazole phosphate moiety of thiamine. We carried out homology modeling for ThiG to understand the structure–function relationship, and the model was refined with MD simulations. The results showed that the model predicted with (α?+?β)₈-fold of synthase family proteins. Molecular docking of ThiG model with substrate DXP showed binding mode and key residues ARG46, ASN69, THR41, and LYS96 involved in the catalysis. First-line anti-tuberculosis drugs were docked with ThiG to identify the inhibition. The report showed the anti-tuberculosis drugs interact well with ThiG which may lead to block thiamin biosynthesis pathway.     

Eco‐friendly,ultrasound‐assisted,and facile synthesis of one‐pot multicomponent reaction of acridine‐1,8(2H,5H)‐diones in an aqueous solvent

A one‐pot, multistep synthesis of acridine‐1,8(2H,5H)‐diones ( 4a–m ) was achieved by three‐component reaction of dimedone ( 1 ) with an aromatic aldehyde ( 2a–m ) and an ammonium acetate ( 3 ) using water as a green solvent without any catalyst and a simple, easily handled, and ultrasonic technique as well as conventional method.     

Novel Tripod Amphiphiles for Membrane Protein Analysis

Integral membrane proteins play central roles in controlling the flow of information and molecules across membranes. Our understanding of membrane protein structures and functions, however, is seriously limited, mainly due to difficulties in handling and analysing these proteins in aqueous solution. The use of a detergent or other amphipathic agents is required to overcome the intrinsic incompatibility between the large lipophilic surfaces displayed by the membrane proteins in their native forms and the polar solvent molecules. Here, we introduce new tripod amphiphiles displaying favourable behaviours toward several membrane protein systems, leading to an enhanced protein solubilisation and stabilisation compared to both conventional detergents and previously described tripod amphiphiles.     

Multi-targeted molecular docking,drug-likeness and ADMET studies of derivatives of few quinoline- and acridine-based FDA-approved drugs for anti-breast cancer activity

Structural Chemistry - Quinoline- and acridine-based drugs are widely used as anti-breast cancer agents. These drugs act through various mechanisms of action; for example, neratinib acts on...