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In this study, the authors use high-throughput virtual screening to design and evaluate a set of non-nucleoside reverse transcriptase inhibitors for binding affinity to the protein reverse transcriptase. These studies have important applications toward HIV therapies.

As cancer continues to take millions of lives worldwide, the need to create effective therapeutics for the disease persists. The kinesin Eg5 assembly motor protein is a promising target for cancer therapeutics as inhibition of this protein leads to cell cycle arrest. Monastrol, a small dihydropyrimidine-based molecule capable of inhibiting the kinesin Eg5 function, has attracted the attention of medicinal chemists with its potency, affinity, and specificity to the highly targeted loop5/α2/α3 allosteric binding pocket. In this work, we employed high-throughput virtual screening (HTVS) to identify potential small molecule Eg5 inhibitors from a designed set of novel dihydropyrimidine analogs structurally similar to monastrol.

In an extensive study of gene mutations, and their resulting effect on protein-protein interactions, Desai and Stork found that HTT-PRPF40B-MECP2 interactions are weakened with progression of Lopes-Maciel-Rodan syndrome.

Molecules which bind to proteins that aggregate abnormally in neurodegenerative diseases could be promising drugs for these diseases. In this study, Zhang, Wu, Zhang, and Dang simulate the binding behavior of various molecules to screen for candidates which could be promising candidates for drug development.

In this study, the authors observe if the symptoms of Rett Syndrome, a neurodegenerative disease in humans, are reflected in Drosophila melanogaster. This was achieved by differentiating the behavior and physical aspects of wild-type flies from flies expressing the full-length MeCP2 gene and the mutated MeCP2 gene (R106W). After conducting these experiments, some of the Rett Syndrome symptoms were recapitulated in Drosophila, and a subset of those were partially ameliorated by the introduction of pifithrin-alpha.

This article investigates differences in gene expression in the brains of patients with and without Parkinson's disease. The authors identify a crucial transcriptional regulator may be a relevant target for future therapeutic treatment for Parkinson's disease.

Wound-healing involves a sequence of events, such as inflammation, proliferation, and migration of different cell types like fibroblasts. Zinc Finger CCCH-type with G-Patch Domain Containing Protein (ZGPAT), encodes a protein that has its main role as a transcription repressor by binding to a specific DNA sequence. The aim of the study was to find out whether inhibiting ZGPAT will expedite the wound healing process by accelerating cell migration. This treatment strategy can provide a key to the development of wound healing strategies in medicine and cellular biology.

Enzyme chemotaxis is a thermodynamic phenomenon in which enzymes move along a substrate concentration gradient towards regions with higher substrate concentrations and can be used to steer nanovehicles towards targets along natural substrate concentrations. In patients with Alzheimer’s disease, a gradient of tau protein forms in the bloodstream. Tau protein is a substrate of the enzyme CDK5, which catalyzes the phosphorylation of tau protein and can travel using chemotaxis along tau protein gradients to increasing concentrations of tau and amyloid-beta proteins. The authors hypothesized that CDK5 would be able to overcome these barriers of Brownian motion and developed a quantitative model using Michaelis-Menten kinetics to define the necessary parameters to confirm and characterize CDK5’s chemotactic behavior to establish its utility in drug delivery and other applications.

DegS is an integral inner membrane protein in E. coli that helps break down misfolded proteins. When it is mutated, there is a large increase in the production of outer membrane vesicles (OMVs), which are thought to play a role in pathogenesis. This study used mutant strains of uropathogenic E. coli (UPEC) to characterize the role of DegS and OMVs on UPEC virulence.

Here, through protein-ligand docking, the authors investigated the effect of the interaction of emodin with serine/threonine kinases, a subclass of kinases that is overexpressed in many cancers, which is implicated in phosphorylation cascades. Through molecular dynamics theyfound that emodin forms favorable interactions with chitosan and chitosan PEG (polyethylene glycol) copolymers, which could aid in loading drugs into nanoparticles (NPs) for targeted delivery to cancerous tissue. Both polymers demonstrated reasonable entrapment efficiencies, which encourages experimental exploration of emodin through targeted drug delivery vehicles and their anticancer activity.