A5106176874- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Bacterial Genetics and Biotechnology
- DNA and Nucleic Acid Chemistry
- Spectroscopy and Quantum Chemical Studies
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Digestive system and related health
- Galectins and Cancer Biology
- Mass Spectrometry Techniques and Applications
- Cell Adhesion Molecules Research
- Ion channel regulation and function
- Cerebrovascular and genetic disorders
- Force Microscopy Techniques and Applications
- Microbial Metabolic Engineering and Bioproduction
- Trypanosoma species research and implications
- Cardiomyopathy and Myosin Studies
University of Warwick
2020-2025
University of Oxford
2019-2021
Integral membrane proteins carry out essential functions in the cell, and their activities are often modulated by specific protein-lipid interactions membrane. Here, we elucidate intricate role of cardiolipin (CDL), a regulatory lipid, as stabilizer complexes. Using silico -designed model protein TMHC4_R (ROCKET) scaffold, employ combination molecular dynamics simulations native mass spectrometry to explore features that facilitate preferential lipid mediate stabilization. We find spatial...
Integral membrane proteins carry out essential functions in the cell, and their activities are often modulated by specific protein-lipid interactions membrane. Here, we elucidate intricate role of cardiolipin (CDL), a regulatory lipid, as stabilizer complexes. Using silico -designed model protein TMHC4_R (ROCKET) scaffold, employ combination molecular dynamics simulations native mass spectrometry to explore features that facilitate preferential lipid mediate stabilization. We find spatial...
Integral membrane proteins carry out essential functions in the cell, and their activities are often modulated by specific protein-lipid interactions membrane. Here, we elucidate intricate role of cardiolipin (CDL), a regulatory lipid, as stabilizer complexes. Using silico -designed model protein TMHC4_R (ROCKET) scaffold, employ combination molecular dynamics simulations native mass spectrometry to explore features that facilitate preferential lipid mediate stabilization. We find spatial...
Abstract Coarse-grained molecular dynamics provides a means for simulating the assembly and interactions of macromolecular complexes at reduced level representation, thereby allowing both longer timescale larger sized simulations. Here, we describe an enhanced fragment-based protocol converting from coarse-grained to atomistic resolution, further refinement analysis. While focus is upon systems that comprise integral membrane protein embedded in phospholipid bilayer, technique also suitable...
The twin arginine transport (Tat) pathway exports folded proteins across the cytoplasmic membranes of prokaryotes and thylakoid chloroplasts. In
Abstract Integral membrane proteins are regulated by specific interactions with lipids from the surrounding bilayer. The structures of protein-lipid complexes can be determined through a combination experimental and computational approaches, but energetic basis these is difficult to resolve. Molecular dynamic simulations provide primary technique estimate free energies interactions. We demonstrate that energetics may reliably reproducibly calculated using three simulation-based approaches:...
Abstract Mycobacterium tuberculosis ( Mtb ) is the causative agent of tuberculosis, a disease that claims ~1.5 million lives annually. The current treatment regime long and expensive, missed doses contribute to drug resistance. There much be understood about cell envelope, complicated barrier antibiotics need negotiate enter cell. Within this plasma membrane ultimate obstacle proposed comprised over 50% mannosylated phosphatidylinositol lipids (phosphatidyl- myo inositol mannosides, PIMs),...
Abstract Integral membrane proteins are localised and/or regulated by lipids present in the surrounding bilayer. Whilst bacteria such as E. coli have relatively simple membranes when compared to eukaryotic cells, there is ample evidence that many bacterial bind specific lipids, especially anionic lipid cardiolipin. Here, we apply molecular dynamics simulations assess binding 42 different inner proteins. Our data reveals a strong asymmetry between leaflets, with marked increase of leaflet...
Abstract Integral membrane proteins carry out essential functions in the cell, and their activities are often modulated by specific protein-lipid interactions membrane. Here, we elucidate intricate role of cardiolipin (CDL), a regulatory lipid, as stabilizer complexes. Using silico -designed model protein TMHC4_R (ROCKET) scaffold, employ combination molecular dynamics simulations native mass spectrometry to explore features that facilitate preferential lipid mediate stabilization. We find...
Abstract Membrane proteins are frequently modulated by specific protein-lipid interactions. The activation of human inward rectifying potassium (hKir) channels phosphoinositides (PI) has been well characterised. Here, we apply a coarse-grained molecular dynamics free-energy perturbation (CG-FEP) protocol to capture the energetics binding PI lipids hKir channels. By using either single- or multi-step approach, establish consistent value for PIP 2 channels, relative bulk phosphatidylcholine...
Abstract Specific interactions of lipids with membrane proteins contribute to protein stability and function. Multiple lipid surrounding a are often identified in molecular dynamics (MD) simulations are, increasingly, resolved cryo-EM densities. Determining the relative importance specific interaction sites is aided by determination binding affinities experimental or simulation methods. Here, we develop method for determining protein-lipid from equilibrium coarse-grained MD using saturation...
ABSTRACT The twin arginine transport (Tat) pathway exports folded proteins across the cytoplasmic membranes of prokaryotes and thylakoid chloroplasts. In Escherichia coli other Gram-negative bacteria, Tat machinery comprises TatA, TatB TatC components. A receptor complex, formed from all three proteins, binds substrates, which triggers organisation recruitment further TatA molecules to form active translocon. polytopic membrane protein forms core harbours two binding sites for...