New insights into protein–protein interaction modulators in drug discovery and therapeutic advance
Protein-protein interactions (PPIs) are fundamental to cellular signaling and transduction
which marks them as attractive therapeutic drug development targets. What were once …
which marks them as attractive therapeutic drug development targets. What were once …
Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide
The connection and causality between cancer and neurodevelopmental disorders have
been puzzling. How can the same cellular pathways, proteins, and mutations lead to …
been puzzling. How can the same cellular pathways, proteins, and mutations lead to …
Tumor-derived RHOA mutants interact with effectors in the GDP-bound state
RHOA mutations are found at diverse residues in various cancer types, implying mutation-
and cell-specific mechanisms of tumorigenesis. Here, we focus on the underlying …
and cell-specific mechanisms of tumorigenesis. Here, we focus on the underlying …
Hydrogen/deuterium exchange mass spectrometry: fundamentals, limitations, and opportunities
Hydrogen/deuterium exchange mass spectrometry (HDX-MS) probes dynamic motions of
proteins by monitoring the kinetics of backbone amide deuteration. Dynamic regions exhibit …
proteins by monitoring the kinetics of backbone amide deuteration. Dynamic regions exhibit …
The value of protein allostery in rational anticancer drug design: an update
R Nussinov, H Jang - Expert Opinion on Drug Discovery, 2024 - Taylor & Francis
Introduction Allosteric drugs are advantageous. However, they still face hurdles, including
identification of allosteric sites that will effectively alter the active site. Current strategies …
identification of allosteric sites that will effectively alter the active site. Current strategies …
[HTML][HTML] Single cell spatial biology over developmental time can decipher pediatric brain pathologies
Pediatric low grade brain tumors and neurodevelopmental disorders share proteins,
signaling pathways, and networks. They also share germline mutations and an impaired …
signaling pathways, and networks. They also share germline mutations and an impaired …
[HTML][HTML] Cell phenotypes can be predicted from propensities of protein conformations
Proteins exist as dynamic conformational ensembles. Here we suggest that the propensities
of the conformations can be predictors of cell function. The conformational states that the …
of the conformations can be predictors of cell function. The conformational states that the …
The allosteric mechanism of mTOR activation can inform bitopic inhibitor optimization
mTOR serine/threonine kinase is a cornerstone in the PI3K/AKT/mTOR pathway. Yet, the
detailed mechanism of activation of its catalytic core is still unresolved, likely due to mTOR …
detailed mechanism of activation of its catalytic core is still unresolved, likely due to mTOR …
CDK2 and CDK4: Cell Cycle Functions Evolve Distinct, Catalysis-Competent Conformations, Offering Drug Targets
Cyclin-dependent kinases (CDKs), particularly CDK4 and CDK2, are crucial for cell cycle
progression from the Gap 1 (G1) to the Synthesis (S) phase by phosphorylating targets such …
progression from the Gap 1 (G1) to the Synthesis (S) phase by phosphorylating targets such …
Capturing Autoinhibited PDK1 Reveals the Linker's Regulatory Role, Informing Innovative Inhibitor Design
PDK1 is crucial for PI3K/AKT/mTOR and Ras/MAPK cancer signaling. It phosphorylates AKT
in a PIP3-dependent but S6K, SGK, and RSK kinases in a PIP3-independent manner. Unlike …
in a PIP3-dependent but S6K, SGK, and RSK kinases in a PIP3-independent manner. Unlike …