B. K. Shoichet

Structure-based discovery of positive allosteric modulators for the calcium sensing receptor

The paper uses structure-based virtual screening to identify novel CaSR PAMs with higher potency and reduced side effects compared to existing drugs.

Colloidal aggregation confounds cell-based Covid-19 antiviral screens

The paper investigates how colloidal aggregation affects cell-based antiviral screens for Covid-19 drugs, finding that aggregation reduces antiviral potency and suggests a non-specific mechanism.

Docking for molecules that bind in a symmetric stack with SymDOCK

SymDOCK is a docking method that exploits symmetry in amyloid fibrils to predict ligand stacking, successfully reproducing known structures and predicting a new one before its determination.

Structure-Based Discovery of a NPFF1R Antagonist with Analgesic Activity

This paper identifies a selective NPFF1R antagonist with analgesic properties, showing enhanced pain relief when combined with morphine and reduced side effects.

Discovery of a functionally selective serotonin 5-HT1A receptor agonist for the treatment of pain

The paper identifies ST171, a selective 5-HT1A receptor agonist effective in pain models without sedation, and elucidates its mechanism through structural and computational analysis.

Structure-based discovery of CFTR potentiators and inhibitors

The paper identifies novel CFTR modulators using molecular docking, electrophysiology, cryo-EM, and medicinal chemistry, discovering potentiators and inhibitors with mid-nanomolar activity.

Large library docking for cannabinoid-1 receptor agonists with reduced side effects

The paper identifies a new cannabinoid-1 receptor agonist with reduced side effects through large library docking and experimental validation.

Structure-based discovery of inhibitors of the SARS-CoV-2 Nsp14 N7-methyltransferase

The paper identifies multiple inhibitors of SARS-CoV-2 Nsp14 N7-methyltransferase using docking strategies, with some showing sub-10 M potency and selectivity.

Large library docking for novel SARS-CoV-2 main protease non-covalent and covalent inhibitors

The paper identifies novel non-covalent and covalent inhibitors of SARS-CoV-2 main protease through virtual docking and experimental validation.

Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 Macrodomain of SARS-CoV-2

The paper computationally designs and experimentally validates potent inhibitors of the SARS-CoV-2 Nsp3 Macrodomain, identifying 160 ligands and 152 crystal structures with submicromolar affinity.

Structure-based Discovery of Conformationally Selective Inhibitors of the Serotonin Transporter

The paper identifies two novel inhibitors of the serotonin transporter that selectively target the inward-open conformation, showing improved potency and reduced off-target effects compared to existing drugs.

Structure-based design of a chemical probe set for the 5-HT5A serotonin receptor

The paper develops a more selective chemical probe set for the 5-HT5A receptor, showing improved selectivity and reduced assay liabilities compared to the existing SB-699551 antagonist.

Colloidal aggregators in biochemical SARS-CoV-2 repurposing screens

This study identifies colloidal aggregators in SARS-CoV-2 drug repurposing screens, showing that many drugs form colloids at therapeutic concentrations, potentially leading to false positive results.

Crystal structures of the σ2 receptor template large-library docking for selective chemotypes active in vivo

This study uses crystal structures of the σ2 receptor to dock and screen a large library, identifying new chemotypes with high affinity and selectivity for the receptor.

Energy Penalties Enhance Flexible Receptor Docking in a Model Cavity

The paper tests flexible receptor docking with energy penalties using MD simulations on T4 Lysozyme L99A, identifying new ligands and confirming their binding through experimental methods.

Phospholipidosis is a shared mechanism underlying the in vitro antiviral activity of many repurposed drugs against SARS-CoV-2

Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives

The paper identifies food and drug additives that inhibit intestinal drug transporters and shows gut bacteria can inactivate these additives, reducing their inhibitory effect.

The Importance of Reverse Translation for Preclinical Off-Target Mitigation: Quantification and Mitigation of Biases in the FDA Adverse Event Reporting System

This paper quantifies and mitigates biases in the FDA Adverse Event Reporting System (FAERS) by mapping drug identifiers to chemical structures, revealing underlying molecular mechanisms of adverse drug reactions.