D. A. Keedy

An expanded view of ligandability in the allosteric enzyme PTP1B from computational reanalysis of large-scale crystallographic data

The paper reanalyzes crystallographic data to identify new ligand-bound states of PTP1B, revealing hidden binding sites and allosteric effects.

High-resolution double vision of the archetypal protein tyrosine phosphatase

This study presents the highest-resolution crystal structure of apo PTP1B, revealing conformational heterogeneity and highlighting how mutations enhance local dynamics.

Native dynamics and allosteric responses in PTP1B probed by high-resolution HDX-MS

This study uses HDX-MS to analyze the dynamics and allosteric responses of PTP1B, revealing how inhibitors affect protein conformation and dynamics beyond their binding sites.

Uncovering Protein Ensembles: Automated Multiconformer Model Building for X-ray Crystallography and Cryo-EM

This paper introduces enhanced qFit software for building multiconformer models from structural biology data, improving accuracy and usability.

Pushed to extremes: distinct effects of high temperature vs. pressure on the structure of an atypical phosphatase

The paper compares the effects of high temperature and pressure on the structure of the phosphatase STEP, revealing distinct structural changes under each condition.

Room-temperature crystallography reveals altered binding of small-molecule fragments to PTP1B

This study compares cryo and room-temperature crystallography of PTP1B with small-molecule fragments, showing RT reveals different binding modes and conformational changes.

Room-temperature serial synchrotron crystallography of apo PTP1B

The paper uses serial synchrotron crystallography to determine the room-temperature structure of apo PTP1B, revealing distinct conformational behavior in the distal allosteric site compared to previous studies.

The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (Mpro)

This study reports high-resolution crystal structures of SARS-CoV-2 Mpro at various temperatures and humidity, revealing temperature-dependent conformational changes and structural features relevant to antiviral drug development.

qFit 3: Protein and ligand multiconformer modeling for X-ray crystallographic and single-particle cryo-EM density maps

qFit 3 automates multiconformer modeling of dynamic proteins from X-ray and cryo-EM data, offering improved efficiency and accessibility.

Model selection for biological crystallography

This paper develops a framework for selecting complex models in biological crystallography using statistical criteria, finding they are less prone to overfitting than traditional methods.

qFit-ligand reveals widespread conformational heterogeneity of drug-like molecules in X-ray electron density maps

qFit-ligand identifies unmodeled ligand conformations in crystal structures, revealing 29% of drug-like molecules exhibit conformational heterogeneity that could improve drug design.

New routes for PTP1B allosteric inhibition by multitemperature crystallography, fragment screening and covalent tethering

The paper identifies a new allosteric site in PTP1B using multitemperature crystallography and fragment screening, showing covalent tethering can inhibit enzyme activity.