A. J. Mulholland

Substrate recognition and selectivity in SARS-CoV-2 main protease: Unveiling the role of subsite interactions through dynamical nonequilibrium molecular dynamics simulations

This study uses dynamical nonequilibrium molecular dynamics simulations to investigate how SARS-CoV-2 main protease dynamically recognizes and responds to substrate binding, revealing key conformational changes and substrate selectivity mechanisms.

Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike

This paper uses D-NEMD simulations to study how the fatty acid site in the glycosylated SARS-CoV-2 spike modulates its structure and function, revealing allosteric networks and the role of glycans.

Electric fields determine carbapenemase activity in class A β-lactamases

The paper investigates how electric fields in class A β-lactamases influence carbapenemase activity using molecular dynamics simulations and identifies key positions that correlate with enzyme efficiency.

Decrypting the languages of allostery in membrane-bound K-Ras4B using four complementary in silico approaches

The paper uses four in silico methods to analyze allostery in K-Ras4B, showing how different 'languages' of allostery change with GTP perturbation.

Cooperative conformational transitions and the temperature dependence of enzyme catalysis

This study investigates the temperature dependence of enzyme catalysis by analyzing MalL and its mutants, showing cooperative conformational transitions and introducing models to explain non-Arrhenius behavior.

Epistasis Arises from Shifting the Rate-Limiting Step during Enzyme Evolution

This study shows that epistasis in enzyme evolution arises from shifting the rate-limiting step in the catalytic cycle, leading to substantial activity enhancements through synergistic mutations.

Antibodies generated in vitro and in vivo elucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine

This study develops a thermostable ADDomer-based nanoparticle vaccine that neutralizes SARS-CoV-2 and cross-reacts with VOCs, demonstrating its potential for nasal administration.

Dynamical nonequilibrium molecular dynamics simulations identify allosteric sites and positions associated with drug resistance in the SARS-CoV-2 main protease

The paper uses D-NEMD simulations to identify allosteric sites and resistance-associated networks in SARS-CoV-2 Mpro.

Tautomer-specific deacylation and {Omega}-loop flexibility explain carbapenem-hydrolyzing, broad-spectrum activity of the KPC-2 β-lactamase

This study identifies how tautomer-specific deacylation and {Omega}-loop flexibility enable KPC-2 β-lactamase to efficiently hydrolyze carbapenems, revealing structural and energetic mechanisms for its broad-spectrum activity.

Molecular dynamics of spike variants in the locked conformation: RBD interfaces, fatty acid binding and furin cleavage sites.

This study uses molecular dynamics simulations to analyze sequence variations in SARS-CoV-2 spike proteins and their effects on receptor binding domain interfaces, fatty acid binding, and furin cleavage site motions across variants.

SARS-CoV-2 spike variants differ in their allosteric response to linoleic acid

This study compares how SARS-CoV-2 spike variants respond to linoleic acid removal using simulations, finding significant differences in allosteric connections that may affect transmissibility and virulence.

Structural and temporal basis for agonism in the α4β2 nicotinic acetylcholine receptor

This study uses molecular dynamics simulations to analyze how full and partial agonists induce different conformational changes in the α4β2 nicotinic acetylcholine receptor, affecting signal propagation.

The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour

This study uses molecular dynamics simulations to show that the fatty acid binding site in the SARS-CoV-2 spike protein influences distant functional regions and variant behavior.

Ligand-induced unfolding mechanism of an RNA G-quadruplex

This study investigates the mechanism by which TMPyP4 induces unfolding of RNA G-quadruplexes using simulations and experiments, revealing a two-state interaction mechanism.

Rigidifying a de novo enzyme increases activity and induces a negative activation heat capacity

This study shows that increasing rigidity in a de novo peroxidase enhances its activity but alters its temperature dependence, resembling natural enzymes.

Allosteric communication in Class A β-lactamases occurs via Cooperative Coupling of Loop Dynamics

This study identifies allosteric communication pathways in Class A β-lactamases using molecular dynamics simulations, showing how amino acid substitutions affect enzyme activity and antibiotic resistance.

Evolution of dynamical networks enhances catalysis in a designer enzyme

This study shows that directed evolution of a designer enzyme introduces dynamical changes that increase activation heat capacity and nonlinearity in temperature dependence through correlated dynamical networks.

Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors

The paper uses molecular simulations to show that the SARS-CoV-2 spike protein's Y674-R685 loop binds to nicotinic acetylcholine receptors, with specific interactions and conformational changes observed across different receptor subtypes.

Dynamical origins of heat capacity changes in enzyme catalysed reactions

The paper uses experiments and simulations to show that heat capacity changes in enzyme-catalyzed reactions can be predicted by molecular dynamics simulations, revealing dynamic changes beyond the active site.