Scott Houliston

Large-scale discovery, analysis, and design of protein energy landscapes

The paper measures conformational fluctuations of protein domains using hydrogen-deuterium exchange mass spectrometry and uses computational modeling to design mutations that stabilize low-stability segments.

Enantioselective Protein Affinity Selection Mass Spectrometry (E-ASMS)

This study introduces E-ASMS, a method to detect weak binders and assess enantioselectivity, identifying 16 binders across 12 human protein targets with confirmed binding mechanisms.

An Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity

The paper describes the enantioselective resolution of a chemical probe targeting CHIKV nsP2 helicase, showing potent antiviral activity for one enantiomer and low activity for the other.

Identification of Direct-acting nsP2 Helicase Inhibitors with Anti-alphaviral Activity

This paper identifies and optimizes oxaspiropiperidine inhibitors targeting nsP2hel, showing nanomolar antiviral activity against multiple alphaviruses.

CACHE Challenge #1: targeting the WDR domain of LRRK2, a Parkinson's Disease associated protein.

The paper evaluates computational hit-finding methods for targeting the WDR domain of LRRK2, a Parkinson's disease protein, finding that diverse strategies yielded weakly potent compounds.

A resource to enable chemical biology and drug discovery of WDR Proteins

The paper develops a resource for discovering ligands for WDR proteins using experimental and computational methods, leading to the identification of drug-like ligands for 9 out of 20 targets.

Dissecting the stability determinants of a challenging de novo protein fold using massively parallel design and experimentation

The paper designs over ten thousand {square}{beta}{beta}{square} proteins, identifies stability determinants, and demonstrates how high-throughput methods can improve protein design success rates.

MLL1 minimal catalytic complex is a dynamic conformational ensemble susceptible to pharmacological allosteric disruption

The paper investigates the dynamic structure of the MLL1 catalytic complex and shows it can be disrupted by pharmacological agents targeting specific interaction sites.