Conformational Switch of a Peptide Provides a Novel Strategy to Design Peptide Loaded Porous Organic Polymer for Pyroptosis Pathway Mediated Cancer Therapy.

While peptide-based drug development is extensively explored, this strategy has limitations due to rapid excretion from the body (or shorter half-life in the body) and vulnerability to protease-mediated degradation. To overcome these limitations, a novel strategy for the development of a peptide-based anticancer agent is introduced, utilizing the conformation switch property of a chameleon sequence stretch (PEP1) derived from a mycobacterium secretory protein, MPT63. The selected peptide is then loaded into a new porous organic polymer (PG-DFC-POP) synthesized using phloroglucinol and a cresol derivative via a condensation reaction to deliver the peptide selectively to cancer cells.

Structure-function analysis of plant G-protein regulatory mechanisms identifies key Gα-RGS protein interactions.

Heterotrimeric GTP-binding protein alpha subunit (Gα) and its cognate regulator of G-protein signaling (RGS) protein transduce signals in eukaryotes spanning protists, amoeba, animals, fungi, and plants. The core catalytic mechanisms of the GTPase activity of Gα and the interaction interface with RGS for the acceleration of GTP hydrolysis seem to be conserved across these groups; however, the RGS gene is under low selective pressure in plants, resulting in its frequent loss. Our current understanding of the structural basis of Gα:RGS regulation in plants has been shaped by Arabidopsis Gα, (AtGPA1), which has a cognate RGS protein.

Phenylpropanoids on the Inhibition of β-Amyloid Aggregation and the Movement of These Molecules through the POPC Lipid Bilayer.

Alzheimer's disease (AD), caused by Aβ aggregation, is a major concern in medical research. It is a neurodegenerative disorder, leading to a loss of cognitive abilities, which is still claiming the lives of many people all over the world. This poses a challenge before the scientific community to discover effective drugs which can prevent such toxic aggregation.

Inhibition of Aβ Peptide Aggregation by Small Molecules and Their Permeation through POPC Lipid Bilayer: Insight from Molecular Dynamics Simulation Study.

Alzheimer's Disease is a rapidly progressing irreversible neurodegenerative disorder characterized by neuronal cell deterioration that endangers human health. With its proper therapeutic treatment being unavailable, several research groups throughout the world are involved in designing efficient drug molecules. However, the elusive mechanism of action of the drugs as well as their debilitating side effects pose major challenges in this regard.

Exploration on the drug solubility enhancement in aqueous medium with the help of endo-functionalized molecular tubes: a computational approach.

One major problem in the pharmaceutical industry is the aqueous solubility of newly developed orally administered drug candidates. More than 50% of newly developed drug molecules suffer from low aqueous solubility. The therapeutic effects of drug molecules are majorly dependent on the bioavailability and, in essence, on the solubility of the used drug molecules.

A computational approach on the stereoselective binding of peptides from aqueous medium with -functionalized molecular tubes.

The need to obtain enantiomerically pure isomers of amino acids and peptides is often realized in the field of biology and in the pharmaceutical industry. Research is underway to devise simple methods for the chiral resolution of amino acids from their racemic mixtures. Inspired by this objective, in our present work, we have computationally shown the possibility of chiral separation of the enantiomeric pairs of two model peptides, namely, (D,L)-aspargine and (D,L)-phenylalanine, in the presence of water.

Translocation of Endo-Functionalized Molecular Tubes across Different Lipid Bilayers: Atomistic Molecular Dynamics Simulation Study.

Various artificial receptors, such as calixarenes, cyclodextrins, cucurbit[n]urils, and their acyclic compounds, pliiar[n]arenes, deep cavitands, and molecular tweezers, can permeate the lipid membranes and they are used as drug carriers to improve the drug solubility, stability, and bioavailability. Inspired by these, we have employed atomistic molecular dynamics simulation to examine the effects of endo-functionalized molecular tubes or naphthotubes (host-1a and host-1b) on seven different types of model lipid bilayers and the permeation properties of these receptors through these model lipid bilayers. Lipid types include six model lipid bilayers (POPC, POPE, DOPC, POPG, DPPE, POPE/POPG) and one realistic membrane (Yeast).

Phase separation property of a hydrophobic deep eutectic solvent-water binary mixture: A molecular dynamics simulation study.

Over the past decade, deep eutectic solvents (DESs) have earned applicability in numerous fields as non-flammable, non-volatile, and greener alternatives to conventional organic solvents. In a first of its kind, a hydrophobic DES composed of a 1:1 mixture of oleic acid and lidocaine was recently reported, possessing a lower critical solution temperature in water. The thermoreversible phase property of this DES-water system was utilized to sequester out dye molecules from their aqueous solutions.

Role of Hydrotropes in Sparingly Soluble Drug Solubilization: Insight from a Molecular Dynamics Simulation and Experimental Perspectives.

Drug molecules' therapeutic efficacy depends on their bioavailability and solubility. But more than 70% of the formulated drug molecules show limited effectiveness due to low water solubility. Thus, the water solubility enhancement technique of drug molecules becomes the need of time.

Switching of Self-Assembly to Solvent-Assisted Assembly of Molecular Motor: Unveiling the Mechanisms of Dynamic Control on Solvent Exchange.

Natural biological molecular motors are capable of performing several biological functions, such as fuel production, mobility, transport, and many other dynamic features. Inspired by these biological motors, scientists effectively synthesized artificial molecular motors to mimic several biological functionalities. Several molecular systems, from sensitive materials to molecular motors, are essential for controlling dynamic processes in larger assemblies.

Computational Study of Encapsulation of Polyaromatic Hydrocarbons by Endo-Functionalized Receptors in Nonpolar Medium.

Polycyclic aromatic hydrocarbons (PAHs) constitute a large group of organic pollutants produced from either natural or artificial sources during the incomplete combustion of fossil fuels or derived from various industrial processes (such as refinery processes of crude petroleum). They are seriously hazardous to human health, and removing them is of major importance. The complexation likeliness with and selective recognition of PAH guests by endo-functionalized molecular tube hosts (host-abu and host-abtu) in a nonpolar medium are investigated using classical molecular dynamics simulation and quantum calculation to probe the factors and the molecular mechanism involved in complexation processes.

Synergistic host-guest hydrophobic and hydrogen bonding interactions in the complexation between endo-functionalized molecular tube and strongly hydrophilic guest molecules in aqueous solution.

The propensity of complex formation of a host, an endo-functionalized naphthotube that has bisnaphthalene cleft architecture (host-1b), with four different strongly neutral hydrophilic guest molecules, namely 1,4-dioxane (14D), acetone, DMSO and DMF, in water is examined using classical molecular dynamics simulations. This type of molecular tube has received significant attention recently due to its usefulness as a supramolecular catalyst and for its ability to selectively recognise biologically and environmentally important neutral molecules in aqueous solution. We sequentially address the role of the different guest molecules in the structural change of host-1b, the role of the host-inserted guest and the water-inserted guest hydrogen bond properties and the host-guest binding free energies in the complex.