Rotation and Self-Assembly Driving NLRP3 Activation.

As a critical sensor protein, NLRP3 detects cellular perturbation caused by diverse exogenous and endogenous stimuli. NLRP3 activation requires domain rotation within the NEK7-bound NLRP3 monomer and assembly. However, a detailed molecular mechanism for NLRP3 assembly and activation remains elusive, particularly in terms of dynamics and energetics.

How Does the Spliceosome Catalyze Intron Lariat Formation? Insights from Quantum Mechanics/Molecular Mechanics Free-Energy Simulations.

The spliceosome catalyzes nuclear pre-mRNA splicing via formation of an intron lariat and is arguably the most complex macromolecular machine in eukaryotic cells. Intron lariat formation is a conservative feature of the splicing reaction for both spliceosomal and group II introns. Despite the importance of the lariat formation in pre-mRNA splicing, an atomic-level understanding of the reaction mechanism remains elusive.

Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD.

Catalytic Mechanism of the Maltose Transporter Hydrolyzing ATP.

We use quantum mechanical and molecular mechanical (QM/MM) simulations to study ATP hydrolysis catalyzed by the maltose transporter. This protein is a prototypical member of a large family that consists of ATP-binding cassette (ABC) transporters. The ABC proteins catalyze ATP hydrolysis to perform a variety of biological functions.

QM/MM investigation of ATP hydrolysis in aqueous solution.

Adenosine-5'-triphosphate (ATP) hydrolysis represents a most important reaction in biology. Despite extensive research efforts, the mechanism for ATP hydrolysis in aqueous solution still remains under debate. Previous theoretical studies often predefined reaction coordinates to characterize the mechanism for ATP hydrolysis in water with Mg(2+) by evaluating free energy profiles through these preassumed reaction paths.

Probing structural determinants of ATP-binding cassette exporter conformational transition using coarse-grained molecular dynamics.

ATP-binding cassette (ABC) exporters pump various substrates across the cell membrane by alternating between inward-facing (IF) and outward-facing (OF) conformations of the transmembrane domains (TMDs). However, the structural determinants of the conformational transition and their functional roles are not fully understood. In this study, we carried out coarse-grained molecular dynamics (CG-MD) simulations with umbrella sampling for the multidrug transporter P-glycoprotein from Caenorhabditis elegans in the presence of the membrane and explicit water molecules.

How does protein architecture facilitate the transduction of ATP chemical-bond energy into mechanical work? The cases of nitrogenase and ATP binding-cassette proteins.

Transduction of adenosine triphosphate (ATP) chemical-bond energy into work to drive large-scale conformational changes is common in proteins. Two specific examples of ATP-utilizing proteins are the nitrogenase iron protein and the ATP binding-cassette transporter protein, BtuCD. Nitrogenase catalyzes biological nitrogen fixation whereas BtuCD transports vitamin B(12) across membranes.