L. Delemotte

PI-(3,5)P2-mediated oligomerization of the endosomal sodium/proton exchanger NHE9

This study reports cryo-EM structures of NhaA and NHE9 with lipid binding at the dimer interface, showing PI(3,5)P2 stabilizes NHE9 oligomerization and enhances activity.

Coevolution-driven method for efficiently simulating conformational changes in proteins reveals molecular details of ligand effects in the beta2AR receptor

This paper introduces a coevolution-driven method to simulate protein conformational changes, revealing ligand effects on the beta2AR receptor's activation and signaling pathways.

The full spectrum of OCT1 (SLC22A1) mutations bridges transporter biophysics to drug pharmacogenomics

This study examines OCT1 mutations to understand their impact on drug response and identifies population-specific allele frequencies linked to LDL cholesterol levels.

Free energy landscapes of KcsA inactivation

This study uses enhanced sampling simulations to analyze the free energy landscape of KcsA inactivation, identifying key residues and force field dependencies in the process.

Modulation of pore opening of Eukaryotic sodium channels by π-helices in S6

This paper investigates how π-helices in S6 helices of eukaryotic sodium channels affect pore conductance, showing that their presence leads to fully conductive states while their absence results in sub-conductance or non-conducting states.

An intracellular hydrophobic nexus is critical for slow deactivation in hERG channels

This study identifies a hydrophobic nexus in hERG channels critical for slow deactivation, showing that altering hydrophobicity at this interface accelerates deactivation and links to long QT syndrome mutations.

Reconstructing the transport cycle in the sugar porter superfamily using coevolution-powered machine learning

The paper uses coevolution analysis and comparative modeling to predict the transport cycle states of the sugar porter superfamily and defines molecular determinants of the cycle.

An α-π transition in S6 shapes the conformational cycle of the bacterial sodium channel NavAb

The paper identifies an α-π helix transition in the S6 helix of NavAb that enables pore opening and contributes to the conformational cycle of the bacterial sodium channel.

Determinants of sugar-induced influx in the mammalian fructose transporter GLUT5

This study shows GLUT5 transitions through an occluded state similar to PfHT1, with fructose binding lowering energetic barriers and enabling fast sugar flux through allosteric coupling.

Markov State Modelling Reveals Heterogeneous Drug-Inhibition Mechanism of Calmodulin

This paper uses Markov state modeling and molecular dynamics simulations to analyze how the drug TFP inhibits CaM by stabilizing different conformations, revealing three distinct binding modes and their effects on CaM structure.

Interplay between VSD, pore and membrane lipids in electromechanical coupling in HCN channels

This study investigates the electromechanical coupling in HCN channels by simulating the interplay between voltage-sensor domains, pore regions, and membrane lipids.

Identification of electroporation sites in the complex lipid organization of the plasma membrane

This study identifies electroporation sites in the plasma membrane by combining simulations, machine learning, and Bayesian analysis, showing pores form in lipid domains with high polyunsaturated lipid density and depend on mechanical properties and electric field polarity.

An open state of a voltage-gated sodium channel involving a π-helix and conserved pore-facing Asparagine

This paper uses molecular modeling and simulations to propose a stable open state model for the NavMs channel, featuring a π-helix and conserved asparagine residue, resolving disputes about its functional annotation.

Allosteric effect of nanobody binding on ligand-specific active states of the β2-Adrenergic Receptor

This study investigates how nanobody binding stabilizes the active state of the β2-adrenergic receptor and modulates ligand affinity through conformational changes and allosteric signaling.

Probing effects of the SARS-CoV-2 E protein on membrane curvature and intracellular calcium

This study investigates the SARS-CoV-2 E protein's effects on membrane curvature and intracellular calcium, using experimental and computational methods.

Identification of ligand-specific G-protein coupled receptor states and prediction of downstream efficacy via data-driven modeling

This study uses molecular dynamics simulations to model GPCR states and predict downstream efficacy based on ligand interactions.

Informing NMR experiments with molecular dynamics simulations to characterize the dominant activated state of the KcsA ion channel

The paper uses molecular dynamics simulations and NMR data to identify the activated state of the KcsA ion channel that best matches experimental SSNMR results.

Functional crosstalk between phosphorylation and disease-causing mutations in the cardiac sodium channel Nav1.5

This paper investigates how phosphorylation and disease-causing mutations interact in Nav1.5, showing that mutations can amplify phosphorylation's impact on channel function and drug sensitivity.

Calmodulin acts as a state-dependent switch to control a cardiac potassium channel opening

The paper shows CaM-VSD interactions act as a state-dependent switch to control KCNQ1 pore opening by modulating PIP2 binding and VSD-pore coupling.

Network analysis reveals how lipids and other cofactors influence membrane protein allostery

The paper extends residue interaction networks to include lipids and small molecules, showing their role in membrane protein allostery using three protein examples.

Mechanism and effects of the skeletal muscle Nav1.4 inhibition by cannabidiol

This study investigates how cannabidiol inhibits Nav1.4 channels in skeletal muscle by modulating membrane elasticity and directly interacting with the channel pore.

Resin-acid derivatives bind to multiple sites on the voltage-sensor domain of the Saker channel

This study identifies three resin-acid binding sites on the Shaker KV channel using molecular dynamics and electrophysiology, showing their role in channel activation.

Molecular insights from conformational ensembles via Machine Learning

This paper applies machine learning to analyze molecular simulations, identifying interpretable features in biomolecular processes like ligand binding and voltage sensing.

Energy landscapes reveal agonist control of GPCR activation via microswitches

The paper uses molecular dynamics simulations to show how agonist binding to GPCRs controls activation through microswitches that couple extracellular and intracellular conformational changes.

Pulsed electric fields create pores in the voltage sensors of voltage-gated ion channels

This study uses molecular dynamics simulations to show that pulsed electric fields create pores in voltage-sensor domains of voltage-gated ion channels, leading to dysfunction and altered ionic currents.

Molecular basis for voltage sensitivity in membrane proteins

The paper introduces a computational method to predict voltage-sensing elements in membrane proteins by analyzing their response to membrane potential changes, identifying residues and ions involved in voltage sensitivity.

Effect of Ca2+ on the promiscuous target-protein binding mechanism of calmodulin

This paper investigates how Ca2+ affects calmodulin's binding mechanism to target proteins, revealing distinct conformational states and binding selectivity through molecular dynamics simulations.

Free energy calculations suggest a mechanism for Na+/K+-ATPase ion selectivity

The paper uses molecular simulations to identify a mechanism for Na+/K+-ATPase ion selectivity changes during conformational transitions.