G. R. Bowman

G protein activation occurs via a largely universal mechanism

The paper uses simulations to study G protein activation mechanisms, finding conserved allosteric pathways and validating their dominance through experimental mutation analysis.

POPSHIFT: A THERMODYNAMICALLY SOUND APPROACH TO ESTIMATE BINDING FREE ENERGIES BY ACCOUNTING FOR LIGAND-INDUCED POPULATION SHIFTS FROM A LIGAND-FREE MSM

The paper introduces PopShift, a method to estimate binding free energies by accounting for ligand-induced population shifts in protein conformations using Markov state models, showing improved accuracy over traditional methods.

Divergent Molecular Phenotypes in Point Mutations at the Same Residue in Beta-Myosin Heavy Chain Lead to Distinct Cardiomyopathies

This study shows that two point mutations at the same residue in beta-myosin heavy chain cause distinct cardiomyopathies through different molecular mechanisms.

Discovery of a cryptic pocket in the AI-predicted structure of PPM1D phosphatase explains the binding site and potency of its allosteric inhibitors

The paper shows that using dynamic simulations with an AlphaFold structure improves the prediction of allosteric inhibitor binding to PPM1D compared to static structures.

Deep Generative Design of Epitope-Specific Binding Proteins by Latent Conformation Optimization

This paper introduces Sculptor, a deep generative algorithm for designing epitope-specific binding proteins by optimizing loop conformations and backbone structures.

Accelerating cryptic pocket discovery using AlphaFold

This study uses AlphaFold to generate structures for cryptic pockets, showing it can sample open states and aid in discovering drug targets, though some remain challenging.

Drug specificity and affinity are encoded in the probability of cryptic pocket opening in myosin motor domains

This paper shows that the probability of cryptic pocket opening in myosin motor domains predicts drug specificity and affinity, using molecular dynamics simulations and Markov state models.

Predicting the locations of cryptic pockets from single protein structures using the PocketMiner graph neural network

The paper introduces PocketMiner, a graph neural network that predicts cryptic pockets in proteins, identifying them accurately and rapidly, expanding the druggable proteome.

A nepenthesin insert allosterically controls catalysis in the malaria parasite protease plasmepsin V

The paper identifies a nepenthesin insert essential for plasmepsin V function in malaria parasites and shows it allosterically regulates catalysis.

Apolipoprotein E4 has extensive conformational heterogeneity in lipid free and bound forms

This study uses single-molecule spectroscopy and molecular dynamics simulations to show that ApoE4 has extensive conformational heterogeneity in both lipid-free and lipid-bound states, differing from previous models.

Intrinsically disordered pathogen effector alters the STAT1 dimer to prevent recruitment of co-transcriptional activators CBP/p300

This study identifies how the parasite Toxoplasma gondii uses the disordered protein TgIST to block STAT1-mediated gene expression by altering STAT1 dimer conformation and preventing activator recruitment.

Bexarotene derivatives modify responses in acute myeloid leukemia

This study screens bexarotene derivatives to identify compounds with enhanced anti-leukemic activity in AML, finding that dual RARA/RXRA activity and structural modifications affect potency and metabolic stability.

Opening of a Cryptic Pocket in β-lactamase Increases Penicillinase Activity

The paper investigates how a cryptic pocket in β-lactamase, formed under the Ω-loop, enhances enzyme activity against penicillin, suggesting excited states can improve function.

SARS-CoV-2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential

This paper investigates how Nsp10 activates Nsp16 and identifies a cryptic pocket in SARS-CoV-2 Nsp16 that could be targeted for pan-coronavirus antivirals.

VirB, a key transcriptional regulator of virulence plasmid genes in Shigella flexneri, forms DNA-binding site dependent foci in the bacterial cytoplasm

The paper investigates the subcellular localization of VirB, a transcriptional regulator of virulence genes in Shigella flexneri, showing that DNA-binding site interactions are required for its formation of discrete cytoplasmic foci.

DiffNets: Self-supervised deep learning to identify the mechanistic basis for biochemical differences between protein variants

DiffNets identifies structural features predicting biochemical differences between protein variants using self-supervised learning.

SARS-CoV-2 Simulations Go Exascale to Capture Spike Opening and Reveal Cryptic Pockets Across the Proteome

The paper uses exascale simulations to study SARS-CoV-2 protein dynamics, revealing cryptic epitopes and conformational changes that inform antiviral target design.

The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA

This study investigates the SARS-CoV-2 nucleocapsid protein's dynamics, disorder, and RNA phase separation using single-molecule spectroscopy and simulations, revealing its multivalent RNA binding properties and phase separation behavior.

A cryptic pocket in Ebola VP35 allosterically controls RNA binding

This study identifies a cryptic pocket in Ebola VP35 that allosterically controls RNA binding, validated through simulations, experiments, and drug-like modifications.

Spatial and temporal alterations in protein structure by EGF regulate cryptic cysteine oxidation

This study identifies three spatiotemporal patterns of cysteine oxidation in response to EGF stimulation, revealing that cryptic cysteines become redox regulated through structural changes induced by EGF.

Conformational distributions of isolated myosin motor domains encode their mechanochemical properties

The paper models conformational distributions of myosin motor domains using molecular dynamics simulations to predict mechanochemical properties better than sequence or structure alone.

Enspara: Modeling molecular ensembles with scalable data structures and parallel computing

Enspara improves the scalability of Markov state models by introducing novel algorithms and data structures for efficient computation.

Cooperative changes in solvent exposure identify cryptic pockets, conformational switches, and allosteric coupling

The paper introduces a method to identify functionally-relevant conformational changes in proteins by analyzing cooperative solvent exposure changes, demonstrating its utility in discovering cryptic allosteric sites.

Simulation of spontaneous G protein activation reveals a new intermediate driving GDP unbinding

The paper simulates G protein activation to identify a new intermediate that drives GDP unbinding, revealing tilting of a helix as the rate-limiting step.

An evolutionary switch in the specificity of an endosomal CORVET tether underlies formation of regulated secretory vesicles in the ciliate Tetrahymena thermophila

The paper identifies an evolutionary switch in the specificity of a CORVET tether in Tetrahymena thermophila that enables the formation of regulated secretory vesicles called mucocysts.