Matthew S. Smith

The paper develops a cooperative binding model for ligands to protein fibrils, relating measured EC50 and IC50 values to intrinsic affinity and cooperativity.

This paper tests the impact of library size and testing scale on virtual screening by comparing results from 1.7 billion vs. 99 million molecule libraries against AmpC β-lactamase, finding improved hit rates and potency with larger libraries.

The paper determines the cryo-EM structure of Alzheimer's disease tau filaments bound by the PET ligand MK-6240, revealing key binding interactions that inform ligand design.

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.

This paper introduces a method to calculate ligand strain energy using torsional populations from the Cambridge Structural Database, improving docking hit rates by filtering strained decoys.

The paper develops probability-based methods for detecting outliers in replicated high-throughput biological data and demonstrates their application using experimental and simulated data.