Jim Warwicker

Prediction of pH-sensing histidine residues in human cells

This study predicts pH-sensing histidine residues in the human proteome using amino acid conservation, structural context, and benchmarking with known pH-sensors.

Charged amino acid propensities and solubility: lysine is elevated at the termini of helices in E. coli proteins.

The paper examines lysine and arginine propensities at helical termini in E. coli proteins, finding lysine enrichment in more soluble proteins.

Outward-facing P-glycoprotein bound to drug displays nucleotide-dependent drug egress mechanism

This study uses simulations to reveal how ATP binding and hydrolysis drive drug egress through P-glycoprotein by coordinating transmembrane domain motions and nucleotide states.

Drug-bound P-glycoprotein reveals nucleotide-dependent ligand pockets and ingress channels

This study uses computational analysis to explore how nucleotide states and ligand binding in P-glycoprotein influence drug transport and allosteric signaling.

Computational investigation suggests that the cell adhesion sub-proteome is enriched for sites of pH-dependence and charge burial, whilst some key intracellular pathways may be shielded from pH fluctuations.

The paper predicts pH-dependent sites in the human proteome, finding enrichment in cell adhesion proteins and shielding of ribosomal/nuclear processes from pH fluctuations.

Nucleotide Asymmetry and Flexible Linker Dynamics Modulate Drug Efflux Cycle of P-glycoprotein, a Computational Study

This study uses computational methods to investigate how nucleotide asymmetry and linker dynamics influence the drug efflux mechanism of P-glycoprotein.

Computational investigation of missense somatic mutations in cancer and potential links to pH-dependence and proteostasis

The paper investigates missense somatic mutations in cancer, focusing on pH-dependence and proteostasis, and finds no clear separation of mutation subsets by pH-sensing potential.

Enrichment of charge-absent regions in phase separated proteins

The paper identifies charge-absent regions in proteins involved in liquid-liquid phase separation and suggests their role in condensate formation through hydrophobic interactions.

Relationship between monomer packing, receptor binding domain pocket status, and pH, in the spike trimer of SARS-CoV-2 variants

The paper examines how monomer packing and receptor binding domain pocket status in SARS-CoV-2 spike proteins relate to pH and mutations like D614G and Omicron variants.

PhosIDP: a web tool to visualize the location of phosphorylation sites in disordered regions

PhosIDP visualizes how phosphorylation affects charge and fold propensity in intrinsically disordered regions, aiding in functional interpretation of phosphorylation effects.

A model for pH coupling of the SARS-CoV-2 spike protein open/closed equilibrium.

The paper models pH-dependent stability of SARS-CoV-2 spike protein conformations, identifying key residues and mutations that influence the open/closed equilibrium.

Predicted pH-dependent stability of SARS-CoV-2 spike protein trimer from interfacial acidic groups

The paper predicts pH-dependent stability of SARS-CoV-2 spike protein trimers, showing acidic sidechains stabilize the locked form at lower pH, with implications for vaccine design.

protein-sol pKa: prediction of electrostatic frustration, with application to coronaviruses

The paper introduces a tool to predict electrostatic frustration in proteins by analyzing protonatable groups, applied to coronaviruses to identify histidine residues affected by acidic pH.

Modelling of pH-dependence to develop a strategy for stabilising mAbs at acidic steps in production

The paper develops a computational model to analyze pH-stability of antibodies and applies it to proteases, identifying design principles for acid-stable proteins.

Charge and hydrophobicity are key features in sequence-trained machine learning models for predicting the biophysical properties of clinical-stage antibodies

The paper develops machine learning models to predict antibody biophysical properties using sequence data, finding that charge and hydrophobicity are key features.

Computational investigation of protein surface polarity and pH-dependence: application to antibodies shows that antibody-antigen interfaces tend to be relatively polar.

The paper develops a web server to predict protein surface polarity and pH/ionic strength dependence, showing antibody-antigen interfaces are as polar as Fab surfaces.