Democratising complex system modelling.

In the contemporary context of an acute need for sustainability and swift response to imminent crises such as global warming, pandemics and economic system disruptions, the focus on responsible decision making, ethical risk assessment and mitigation at all organizational levels is an overarching goal. Our aim is to introduce a deterministic method for investigating the stability of complex systems, in order to find the most important elements of such systems and their impact on different scenarios. The novelty of the current approach lies in its compact format and intuitive nature, designed to accommodate a limited amount of computational resources.

Flexibility in the Periplasmic Domain of BamA Is Important for Function.

The β-barrel assembly machine (BAM) mediates the biogenesis of outer membrane proteins (OMPs) in Gram-negative bacteria. BamA, the central BAM subunit composed of a transmembrane β-barrel domain linked to five polypeptide transport-associated (POTRA) periplasmic domains, is thought to bind nascent OMPs and undergo conformational cycling to catalyze OMP folding and insertion. One model is that conformational flexibility between POTRA domains is part of this conformational cycling.

Structure-Based Assignment of Ile, Leu, and Val Methyl Groups in the Active and Inactive Forms of the Mitogen-Activated Protein Kinase Extracellular Signal-Regulated Kinase 2.

Resonance assignments are the first step in most NMR studies of protein structure, function, and dynamics. Standard protein assignment methods employ through-bond backbone experiments on uniformly (13)C/(15)N-labeled proteins. For larger proteins, this through-bond assignment procedure often breaks down due to rapid relaxation and spectral overlap.

Dynamics of protein kinases: insights from nuclear magnetic resonance.

Protein kinases are ubiquitous enzymes with critical roles in cellular processes and pathology. As a result, researchers have studied their activity and regulatory mechanisms extensively. Thousands of X-ray structures give snapshots of the architectures of protein kinases in various states of activation and ligand binding.

Slow inhibition and conformation selective properties of extracellular signal-regulated kinase 1 and 2 inhibitors.

The mitogen-activated protein (MAP) kinase pathway is a target for anticancer therapy, validated using inhibitors of B-Raf and MAP kinase kinase (MKK) 1 and 2. Clinical outcomes show a high frequency of acquired resistance in patient tumors, involving upregulation of activity of the MAP kinase, extracellular signal-regulated kinase (ERK) 1 and 2. Thus, inhibitors for ERK1/2 are potentially important for targeted therapeutics against cancer.