M. C. Thompson

Design of efficient artificial enzymes using crystallographically-enhanced conformational sampling

This paper designs artificial enzymes with high catalytic efficiency using crystallography-enhanced computational methods, achieving improvements comparable to directed evolution.

Changes in an Enzyme Ensemble During Catalysis Observed by High Resolution XFEL Crystallography

The paper uses XFEL crystallography to observe conformational changes in an enzyme during catalysis, revealing ionization-linked dynamics that control catalytic activity.

Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase

This study characterizes the pH-specific enzymatic activity and ligand binding of mouse AMCase using structural and computational methods, revealing dual activity optima at pH 2 and 7.

Computational remodeling of an enzyme conformational landscape for altered substrate selectivity

This study computationally redesigns an enzyme's conformational landscape to enhance catalytic efficiency with a non-native substrate, achieving up to 1900-fold selectivity switch.

Mapping Protein Dynamics at High-Resolution with Temperature-Jump X-ray Crystallography

This study uses temperature-jump X-ray crystallography to observe atomic-scale protein motions in lysozyme, showing how vibrations evolve into functional movements and how inhibitors alter these dynamics.

The mechanisms of catalysis and ligand binding for the SARS-CoV-2 NSP3 macrodomain from neutron and X-ray diffraction at room temperature

This study determines the crystal structures of SARS-CoV-2 NSP3 macrodomain using neutron and X-ray diffraction, revealing insights into its catalytic mechanism and ligand binding.

Accurately positioning functional residues with robotics-inspired computational protein design

This paper introduces two computational methods for accurately positioning functional residues in proteins and validates them by redesigning enzyme active sites.

An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation

This paper develops a potent synthetic nanobody that neutralizes SARS-CoV-2 by locking its Spike protein in an inactive conformation, enabling aerosol delivery as a prophylactic or therapeutic agent.

Evolution of an enzyme conformational ensemble guides design of an efficient biocatalyst

The paper uses X-ray crystallography to study conformational changes in an evolved enzyme, leading to the design of a more efficient biocatalyst by focusing on active-site mutations.

Mix-and-inject XFEL crystallography reveals gated conformational dynamics during enzyme catalysis

This study uses mix-and-inject XFEL crystallography to observe conformational changes in isocyanide hydratase during catalysis, showing how cysteine modification affects enzyme dynamics and function.

Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals

This study compares serial X-ray crystallography and MicroED for determining structures from small macromolecular crystals, highlighting their strengths and challenges.

Aggregated and hyperstable damage-associated molecular patterns are released during ER stress to modulate immune function

The paper shows chronic ER stress releases protease-resistant DAMPs that activate dendritic cells and drive persistent inflammation.

Temperature-Jump Solution X-ray Scattering Reveals Distinct Motions in a Dynamic Enzyme

This study uses temperature-jump X-ray scattering to analyze dynamic motions in cyclophilin A, revealing two distinct relaxation processes linked to substrate specificity and catalytic turnover.

Flexibility and design: conformational heterogeneity along the evolutionary trajectory of a redesigned ubiquitin

This study shows that increasing flexibility in designed proteins can help escape local minima during evolution, using redesigned ubiquitin variants with improved binding affinity to USP7.