Impact of the Cellular Environment on Adenosine Triphosphate Conformations.
Meredith M RickardHaolin LuoAshley De LioMartin GruebeleTaras V PogorelovPublished in: The journal of physical chemistry letters (2022)
The cytoplasm is an environment crowded by macromolecules and filled with metabolites and ions. Recent experimental and computational studies have addressed how this environment affects protein stability, folding kinetics, and protein-protein and protein-nucleic acid interactions, though its impact on metabolites remains largely unknown. Here we show how a simulated cytoplasm affects the conformation of adenosine triphosphate (ATP), a key energy source and regulatory metabolite present at high concentrations in cells. Analysis of our all-atom model of a small volume of the Escherichia coli cytoplasm when contrasted with ATP modeled in vitro or resolved with protein structures deposited in the Protein Data Bank reveals that ATP molecules bound to proteins in cell form specific pitched conformations that are not observed at significant concentrations in the other environments. We hypothesize that these interactions evolved to fulfill functional roles when ATP interacts with protein surfaces.
Keyphrases
- protein protein
- small molecule
- escherichia coli
- binding protein
- amino acid
- induced apoptosis
- oxidative stress
- electronic health record
- mass spectrometry
- transcription factor
- molecular dynamics simulations
- signaling pathway
- machine learning
- single molecule
- single cell
- artificial intelligence
- mesenchymal stem cells
- biofilm formation
- quantum dots
- multidrug resistant
- pseudomonas aeruginosa
- bone marrow
- cystic fibrosis
- deep learning