Adrian John Mulholland

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.

De Novo Design of Flavoproteins with Controlled Excited State Dynamics

This paper designs de novo flavoproteins with controlled excited state dynamics using computational methods and experimental validation.

Cancer-associated mutations reconfigure dynamical responses in EGFR kinase

This study uses D-NEMD simulations to show how cancer mutations in EGFR alter allosteric communication networks and signal propagation within the kinase domain.

Machine learned potentials with electrostatic embedding accurately capture Kemp eliminase reactivity

The paper trains an ML/MM model to accurately predict reaction barriers in Kemp elimination, capturing experimental differences between designed and evolved enzymes.

Evolution promotes transition-state-like conformations with enhanced basicity and electric fields in the substrate complex of a designer enzyme

This study shows directed evolution improves a designed enzyme by enhancing its transition-state-like conformation, reducing reaction barriers through desolvation and electric field organization.

Redox Control of S-sulfocysteine Formation in Adenosine Phosphosulfate Reductase

This study investigates how the redox state of an iron-sulfur cluster in APSR from Pseudomonas aeruginosa influences catalytic activity and substrate binding through molecular simulations.

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.

Porphyrin driven redox tuning in structurally defined de novo heme proteins

This paper designs redox proteins with tunable electron transfer properties by replacing heme B with non-natural metalloporphyrins, achieving redox potential modulation of over 400 mV.

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.

Correlated dynamics, reactive conformations and non-Arrhenius behaviour in the temperature-dependence of enzyme activity: triosephosphate isomerase

This study investigates the temperature dependence of triosephosphate isomerase activity using experiments and simulations, revealing non-Arrhenius behavior and dynamical differences between enzymes from different organisms.

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.

pH-induced structural changes in SARS-CoV-2 spike variants

This study uses D-NEMD simulations to show how pH changes induce variant-specific conformational changes in SARS-CoV-2 spike proteins, affecting their stability and entry mechanisms.

Effective sequence-to-expression prediction for a model membrane protein using machine learning and computational protein design

The paper uses machine learning to predict membrane protein expression from sequence data, achieving high accuracy and guiding protein engineering improvements.

AI.zymes - A modular platform for evolutionary enzyme design

AI.zymes improves enzyme design by integrating multiple algorithms in an evolutionary framework, enhancing catalytic activity through iterative selection and design.

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.

Double crossed? Structural and computational studies of an unusual crosslinked heme in Methylococcus capsulatus cytochrome P460

This study identifies a double crosslink between lysine and heme in Methylococcus capsulatus cytochrome P460 using structural biology and QM/MM simulations.

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.

Photovoltaic enzymes by design and evolution

This paper designs and evolves photoenzymes to enhance photocurrent generation for biohybrid photovoltaic devices.

Structural basis for cell-type specific evolution of viral fitness by SARS-CoV-2

This study investigates how the BriS{Delta} variant of SARS-CoV-2 affects spike structure, function, and infectivity across different cell types.

Beneficial substrate partitioning boosts non-aqueous catalysis in de novo enzyme-alginate beads

This paper demonstrates that encapsulating a de novo heme-containing enzyme in calcium-alginate beads enhances its catalytic activity in non-aqueous solvents through substrate partitioning and enables enzyme recovery.

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.

Precision design of single and multi-heme de novo proteins

The paper designs and validates de novo proteins with single and multi-heme binding capabilities, achieving atomic-level structural resolution for functional engineering.