Speaker
Description
Proteins are the most ubiquitous biomolecules found in nature. Proteins are responsible for catalyzing reactions, transducing signals, structural properties, and much more. During their lives, proteins are found in various environments. It is not rare that proteins are found in enclosed spaces, such as pores, channels, and tunnels. For instance, in the first seconds of their existence, proteins are confined to the exit tunnel of the ribosome, the cell’s protein assembler. When in such spaces, proteins behave differently than when free in solvent. One of the simplest environments to mimic a confined space and study those differences is the carbon nanotube (CNT).
In this work, an automated pipeline was developed to emulate the growth of a peptide in confined environments through all atom molecular dynamic (MD) simulations and computational alchemy. By using the pipeline, we can observe the interactions and forces that are relevant in that environment after the addition of every amino acid.
Starting with a model enclosed space, a CNT with a 1.2 nm diameter, we performed several elongations with different polypeptide sequences (polyalanine, polyserine, polyglycine). The CNT was treated as an infinite structure in the elongation axis to avoid finite system interactions. 12 elongations (replicates) were performed per sequence, with 10 ns of free simulation per added amino acid (70 ns per elongation). Different starting points were randomly selected to ensure a better sampling of the conformational space. To evaluate the trajectories obtained, the end to end distance, radius of gyration, Root-Mean-Square Deviation (RMSD), intramolecular interactions, intermolecular interactions and the rate of progress of the peptide through the CNT were measured and compared. Smaller side chain amino acids, such as glycine, were shown to diffuse faster than slightly more complex side chains, like serine. It was also seen that the end to end distance was much larger in peptides which contained less intramolecular interactions. Furthermore, simpler amino acids moved through the CNT faster than more complex amino acids. This shows that more intramolecular interactions lead to shorter end to end distances, slower elongation rates and, therefore, to a slower progression of the peptide through the CNT. By having this data, and expanding to other amino acids, sequences, and CNT sizes, it would be possible to shed light on the elongation process of proteins in confined spaces, such as the ribosome, with atomistic resolution.
