Howook Hwang

Results of a Large-Scale Study of the Binding of 50 Type II Inhibitors to 348 Kinases: The Role of Protein Reorganization

Vardan H. Vardanyan, Allan Haldane, Howook Hwang, Dilek Coskun et autres

Protein kinases constitute the second largest class of drug targets, most prominently in cancer therapy. In this work, we focus on type II kinase inhibitors that bind to the "classical" inactive conformation. We analyze binding affinities of 50 type II inhibitors across …

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Accelerating Lead Optimization away from Anti-Targets: Navigating the Structural Complexity of Promiscuous ADMET Proteins

Howook Hwang, Mee Shelley, Andrew Placzek, Kevin R. DeMarco et autres

The development of a small-molecule suitable for clinical use involves optimization of ligand binding to an identified target protein but also frequently the reduction of binding to a variety of anti-target proteins known to pose translational risk. These anti-targets, often referred to …

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Structurally Enabling ADMET Anti-Targets via Induced Fit Docking and Free Energy Perturbation

Howook Hwang, Mee Shelley, Andrew Placzek, Kevin R. DeMarco et autres

The development of a small-molecule suitable for clinical use involves optimization of ligand binding to an identified target protein but also frequently the reduction of binding to a variety of anti-target proteins known to pose translational risk. These anti-targets, often referred to …

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Structurally Enabling ADMET Anti-Targets via Induced Fit Docking and Free Energy Perturbation

Howook Hwang, Mee Shelley, Andrew Placzek, Kevin R. DeMarco et autres

The development of a small-molecule suitable for clinical use involves optimization of ligand binding to an identified target protein but also frequently the reduction of binding to a variety of anti-target proteins known to pose translational risk. These anti-targets, often referred to …

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Results of a large scale study of the binding of 50 type II inhibitors to 348 kinases: The role of protein reorganization

Vardan H. Vardanyan, Allan Haldane, Howook Hwang, Dilek Coskun et autres

Kinase family proteins constitute the second largest protein class targeted in drug development efforts, most prominently to treat cancer, but also several other diseases associated with kinase dysfunction. In this work we focus on type II kinase inhibitors which bind to the …

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A Novel CREBBP/p300 Activator, YF2, Enhances Cytotoxic and Immune-Mediated Responses in B-Cell Lymphoma

Ted B. Piorczynski, Yuxuan Liu, Brian Estrella, Edd C. Ricker et autres

Abstract Germinal center B-cell lymphomas frequently exhibit monoallelic loss-of-function mutations in the histone acetyltransferases CREBBP and p300, which contribute to lymphoma development, disrupt normal germinal center biology, and promote immune evasion. This study evaluates YF2, a histone acetyltransferase activator that increases CREBBP/p300 …

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Enabling structure-based drug discovery utilizing predicted models

Edward B. Miller, Howook Hwang, Mee Shelley, Andrew Placzek et autres

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PrePCI : A structure‐ and chemical similarity‐informed database of predicted protein compound interactions

Stephen J. Trudeau, Howook Hwang, Deepika Mathur, Kamrun Begum et autres

We describe the Predicting Protein-Compound Interactions (PrePCI) database which comprises over 5 billion predicted interactions between 6.8 million chemical compounds and 19,797 human proteins. PrePCI relies on a proteome-wide database of structural models based on both traditional modeling techniques and the AlphaFold …

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PrePCI: A structure- and chemical similarity-informed database of predicted protein compound interactions

Stephen J. Trudeau, Howook Hwang, Deepika Mathur, Kamrun Begum et autres

Abstract We describe the Predicting Protein Compound Interactions (PrePCI) database which comprises over 5 billion predicted interactions between nearly 7 million chemical compounds and 19,797 human proteins. PrePCI relies on a proteome-wide database of structural models based on both traditional modeling techniques …

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Community-Wide Assessment of Protein-Interface Modeling Suggests Improvements to Design Methodology

Timothy A. Whitehead, Thom Vreven, Şefik Kerem Ovalı, Jacob E. Corn et autres

The CAPRI and CASP prediction experiments have demonstrated the power of community wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring …

Strategy for Overcoming Crebbp and EP300 Mutations in Lymphoma: Development of First-in-Class HAT Activators

Yuxuan Liu, Jole Fiorito, Yulissa Gonzalez, Brian Estrella et autres

Epigenetic dysregulation is a hallmark of germinal center derived B cell lymphomas. In particular, the monoallelic mutations in histone acetyltransferases (HATs), p300 and CBP are present in approximately 40% of DLBCL and FL patients. The haploinsufficiency of CBP leads to loss of …

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Structure-based prediction of ligand–protein interactions on a genome-wide scale

Howook Hwang, Fabian Dey, Donald Petrey, Barry Honig

We report a template-based method, LT-scanner, which scans the human proteome using protein structural alignment to identify proteins that are likely to bind ligands that are present in experimentally determined complexes. A scoring function that rapidly accounts for binding site similarities between …

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