Speaker
Description
Proteins are the most ubiquitous biomolecules in nature. In the first seconds of their existence, proteins are confined to the exit tunnel of the ribosome, the cell’s protein assembler. Under confinement, proteins behave differently than when free in aqueous solution. The principles of protein translocation through the confined space have been the target of previous studies. The difference of the impact of the pulling motion vs the pushing motion on the structure, however, have been given less attention. Given that a new amino acid is placed on the P-site and likely pushes on the nascent peptide chain towards tunnel exit, pulling the peptide, as used in previous studies, might not be realistic. In this work, the impact caused by pulling and pushing on the peptide structure was assessed using one of the simplest structures to mimic confined spaces, the carbon nanotube (CNT). We carried out multiple non-equilibrium molecular dynamics simulations (NEMDs) of three uncharged 10-residue homopeptides (alanine, serine, glycine). Three different loading rates (both for pulling and pushing) were tested: 1 pN/ps, 0.1 pN/ps, and 0.01 pN/ps. C-terminal or N-terminal peptide residues were used as anchors for the force probe. With this, we have a wide range of scenarios to assess the impact on the structure of the peptides (end to end distance, radius of gyration, intramolecular interaction, secondary structure content, RMSD). Pulling, unlike pushing, caused the end to end distance and gyration to increase through the simulations, suggesting some impact on the peptide structure. Understanding how proteins behave under confinement with different force probes and motions may help us understand their dynamics in biology-relevant environments and approach them with improved knowledge.
