The Keedy Lab

Publications

Perdikari A*, Woods VA*, Ebrahim A*, Lawler K, Bounds R, Singh NI, Mehlman (Skaist) T, Riley BT, Sharma S, Morris JW, Keogh JM, Henning E, Smith M, Farooqi IS**, DA Keedy** (** co-corresponding authors). Structures of human PTP1B variants reveal allosteric sites to target for weight loss therapy. bioRxiv preprint. 2024.


Chartier CA, Woods VA, Xu Y, van Vlimmeren AE, Jovanovic M, McDermott AE, Keedy DA, Shah NH. Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction. bioRxiv preprint. 2024.

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Wankowicz SA, Ravikumar A, Sharma S, Riley BT, Raju A, Hogan D, van den Bedem H, Keedy DA, Fraser JS. Automated multiconformer model building for X-ray crystallography and cryo-EM. eLife. 2024.


Mehlman (Skaist) T, Ginn HM, Keedy DA. An expanded trove of fragment-bound structures for the allosteric enzyme PTP1B from computational reanalysis of large-scale crystallographic data. Structure. 2024.


Woods VA, Abzalimov RR, Keedy DA. Native dynamics and allosteric responses in PTP1B probed by high-resolution HDX-MS. Protein Science. 2024.


Wallach I, …, Keedy DA, …, Smith KS, …, Singh N, …, Hossain S, …, Dzhumaev S, …, Azeem SM, …, Mehlman T, …, Woods VA…, Heifets A (688 total authors). AI is a viable alternative to high throughput screening: a 318-target study. Scientific Reports. 2024.

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Guerrero L*, Ebrahim A*, Riley BT, Kim M, Huang Q, Finke AD, Keedy DA. Pushed to extremes: distinct effects of high temperature versus pressure on the structure of STEP. Communications Biology. 2024.


Sharma S, Mehlman (Skaist) T, Sagabala RS, Boivin B, Keedy DA. High-resolution double vision of the allosteric phosphatase PTP1B. Acta Cryst F. 2024.

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Cavender CE, Case DA, Chen JCH, Chong LT, Keedy DA, Lindorff-Larsen K, Mobley DL, Ollila OHS, Oostenbrink C, Robustelli P, Voelz VA, Wall ME, Wych DC, Gilson MK. Structure-Based Experimental Datasets for Benchmarking of Protein Simulation Force Fields. arXiv preprint. 2023.


Mehlman (Skaist) T, Biel JT, Azeem SM, Nelson ER, Hossain S, Dunnett LE, Paterson NG, Douangamath A, Talon R, Axford D, Orins H, von Delft F, Keedy DA. Room-temperature crystallography reveals altered binding of small-molecule fragments to PTP1B. eLife. 2023.


Richardson JS, Moriarty NW, Keedy DA. Fitting Tip #23 - Alternate conformations always want to spread. Computational Crystallography Newsletter. 2023.


Sharma S, Ebrahim A, Keedy DA. Room-temperature serial synchrotron crystallography of the human phosphatase PTP1B. Acta Cryst F. 2023.


Ebrahim A*, Riley BT*, Kumaran D, Andi B, Fuchs MR, McSweeney S, Keedy DA. The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (Mpro). IUCrJ. 2022.


Riley BT, Wankowicz SA, de Oliveira SHP, van Zundert GCP, Hogan DW, Fraser JS, Keedy DA*, van den Bedem H* (* co-corresponding authors). qFit 3: Protein and ligand multiconformer modeling for X-ray crystallographic and single-particle cryo-EM density maps. Protein Science. 2021.


Keedy DA. Journey to the center of the protein: allostery from multitemperature multiconformer X-ray crystallography. Acta Cryst D. 2019.

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van Zundert GCP*, Hudson BM*, Oliveira SHP, Keedy DA, Fonseca R, Heliou A, Suresh P, Borrelli K, Day T, Fraser JS, van den Bedem H. qFit-ligand reveals widespread conformational heterogeneity of drug-like molecules in X-ray electron density maps. Journal of Medicinal Chemistry. 2018.


Babcock NS, Keedy DA, Fraser JS, Sivak DA. Model selection for biological crystallography. bioRxiv preprint. 2018.

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Keedy DA*, Hill ZB*, Biel JT, Kang E, Rettenmaier TJ, Brandao-Neto J, Pearce NM, von Delft F, Wells JA, Fraser JS. An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering. eLife. 2018.


Williams CJ, Headd JJ, Moriarty NW, Prisant MG, Videau LL, Deis LN, Verma V, Keedy DA, Hintze BJ, Chen VB, Jain S, Lewis SM, Arendall WB 3rd, Snoeyink J, Adams PD, Lovell SC, Richardson JS, Richardson DC. MolProbity: More and better reference data for improved all-atom structure validation. Protein Science. 2018.


Russi S, González A, Kenner LR, Keedy DA, Fraser JS, van den Bedem H. Conformational variation of proteins at room temperature is not dominated by radiation damage. Journal of Synchrotron Radiation. 2017.

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Cimermancic P, Weinkam P, Rettenmaier TJ, Bichmann L, Keedy DA, Woldeyes RA, Schneidmann D, Demerdash ONA, Mitchell JC, Wells JA, Fraser JS, Sali A. CryptoSite: Expanding the druggable proteome by characterization and prediction of cryptic binding sites. Journal of Molecular Biology. 2016


Keedy DA. Conformational and connotational heterogeneity: A surprising relationship between protein structural flexibility and puns. Proteins: Structure, Function, and Bioinformatics. 2015.

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Keedy DA, Fraser JS, van den Bedem H. Exposing hidden alternative backbone conformations in X-ray crystallography using qFit. PLOS Computational Biology. 2015.


Keedy DA*, Kenner LR*, Warkentin M*, Woldeyes RA*, Hopkins JB, Thompson MC, Brewster AS, Van Benschoten AH, Baxter EL, Uervirojnangkoorn M, McPhillips SE, Song J, Alonso-Mori R, Holton JM, Weis WI, Brunger AT, Soltis SM, Lemke H, Gonzalez A, Sauter NK, Cohen AE, van den Bedem H, Thorne RE, Fraser JS. Mapping the Conformational Landscape of a Dynamic Enzyme by Multitemperature and XFEL Crystallography. eLife. 2015.


Keedy DA, van den Bedem H, Sivak DA, Petsko GA, Ringe D, Wilson MA, Fraser JS. Crystal Cryocooling Distorts Conformational Heterogeneity in a Model Michaelis Complex of DHFR. Structure. 2014.


Keedy DA. Using Protein-Likeness to Validate Conformational Alternatives. PhD Thesis. 2012.


For Dr. Keedy’s full publication list, see his Google Scholar profile.