JAMES M. SPENCER

Active site electrostatic effects modulate DBO inhibitor potency against OXA-48 variants

This paper investigates how electrostatic effects in the active site influence the potency of DBO inhibitors against OXA-48 variants using computational simulations.

Structure and dynamics of Burkholderia pseudomallei OXA-57, a distinctive low-efficiency class D β-lactamase with carbapenem-hydrolyzing activity

This paper characterizes OXA-57, a class D β-lactamase from Burkholderia pseudomallei, showing its activity against penicillins and cephalosporins, limited carbapenem hydrolysis, and structural insights into its mechanism.

A transition state-like acylenzyme conformation distinguishes carbapenemase activity in class A β-lactamases

This study uses molecular dynamics simulations to identify structural features distinguishing carbapenemase activity in class A β-lactamases.

Enhanced Target Binding by Leritrelvir Restores Dimerization of Mpro Mutants and Mitigates Drug Resistance

This study evaluates leritrelvir's effectiveness against Mpro variants with resistance mutations, showing it restores dimerization and maintains inhibitory activity better than nirmatrelvir.

Drop on fixed target reaction initiation approach for serial and time resolved crystallography

This paper describes a drop on fixed target method for time-resolved serial crystallography, tested with enzymes to improve measurement consistency across facilities.

Hydrogen-bonding changes cause differences in imipenem breakdown activity in OXA-48 variants

This study identifies how hydrogen-bonding changes in OXA-48 variants affect imipenem hydrolysis efficiency and resistance.

Acyl-enzyme dynamics, tautomerisation and hydration regulate turnover of carbapenem antibiotics by the OXA-48 β-lactamase

This study investigates how acyl-enzyme tautomerisation, dynamics, and hydration affect carbapenem antibiotic turnover by OXA-48 β-lactamase using X-ray crystallography and molecular dynamics simulations.

Time-resolved ligand dynamics revealed in a β-lactamase using room-temperature serial crystallography

This study uses room-temperature serial crystallography to observe time-dependent ligand dynamics of the β-lactamase CTX-M-15 with avibactam, revealing conformational changes critical for inhibitor reformation.

A dynamical-nonequilibrium molecular dynamics (D-NEMD) alanine scanning approach for identifying allosteric positions in proteins

This paper introduces a D-NEMD method to identify allosteric positions in proteins by analyzing long-range structural responses to alanine substitutions, validated on KPC-2 beta-lactamase.

Droplet on Demand Tape Drive and XES Prototypes for Time-Resolved Serial Crystallography at VMXi, Diamond Light Source

The paper demonstrates proof of concept for combined droplet on demand serial crystallography and XES experiments at a synchrotron beamline.

Mechanistic Basis for Inhibition of the Extended Spectrum Class A b-Lactamase GES-1 by Tazobactam and Enmetazobactam

This paper investigates how enmetazobactam and tazobactam inhibit GES-1, an ESBL, revealing structural and mechanistic differences in their acyl-enzyme complexes.

Electrostatic interactions define nacubactam potency against OXA-48-like β-lactamases

This paper compares the potency of nacubactam and avibactam against OXA-48-like β-lactamases, finding that nacubactam is less potent due to electrostatic repulsion with Arg214.

Dynamical Responses Predict a Distal Site that Modulates Activity in an Antibiotic Resistance Enzyme

The paper uses dynamical simulations and experiments to identify a distal site in an antibiotic resistance enzyme that modulates activity when mutated.

Discovery of SARS-CoV-2 Mpro Peptide Inhibitors from Modelling Substrate and Ligand Binding

The paper models SARS-CoV-2 Mpro substrate and ligand binding to identify new inhibitor opportunities through computational analysis of binding interactions.