RESEARCH: CANCER
FOLDING PROJECT #18929 PROFILE

This project studies lasso peptides, unique protein-like molecules with potential medical uses like fighting cancer or infections. Scientists aren't sure exactly how these peptides form their distinctive shape, so they'll use computer simulations to understand the process and explore how to create new ones for medicine.

Lasso peptides are ribosomally synthesized and post-translationally modified peptide (RiPP) natural products that display a unique lariat-like, threaded conformation.

Some lasso peptides have been shown to bind human cell-surface receptors and exhibit anticancer properties, while others display antibacterial or antiviral bioactivities.

So studies on the lasso peptide synthesis will significantly facilitate the discovery and application of new drugs. Specifically, previous studies show that the unique lasso topology is formed by a macrolactam ring that is threaded by the C-terminal tail.

While not proven yet, the threading cannot occur after the ring formation.

The general proposed mechanism is that lasso peptide first form a prefolded lariat-like structure, then lasso peptide cyclase catalyzes the ring closure achieved by an isopeptide bond formed between the N-terminal α-amino group of a glycine, alanine, serine, or cysteine and the carboxylic acid side chain of an aspartate or glutamate, which can be located at positions 7, 8, or 9 of the amino acid sequence.

However, MD study on lasso peptide topology is very less and the detailed function of lasso peptide cyclase and the molecular mechanism of the whole lasso peptide cyclization process are not clear.

Therefore, in this study, we will perform Molecular Dynamic simulations for the system of lasso peptide or peptide with cyclase enzyme to explore lasso peptide topology and the cyclization mechanism.

Lasso peptides

Ribosomally synthesized and post-translationally modified peptides with a unique lariat-like structure.

Lasso peptides are a type of natural product made by bacteria. They have a special shape that looks like a lasso, and they can be used to fight cancer, bacteria, or viruses.

RiPP

Ribosomally Synthesized and Post-translationally Modified Peptides

RiPP stands for Ribosomally Synthesized and Post-translationally Modified Peptides. They are a class of peptides that are made by ribosomes (the protein factories in cells) and then modified after they are made.

Macrolactam ring

A large cyclic amide formed by a reaction between an amine and a carboxylic acid group.

A macrolactam ring is a type of ring structure found in some peptides. It is made when a nitrogen atom (amine) reacts with a carbon atom (carboxylic acid) to form a bond.

Isopeptide bond

A covalent bond formed between the carboxyl group of one amino acid and an amino group on another amino acid.

An isopeptide bond is a special type of chemical bond that connects two amino acids. It helps to form the structure of some important molecules in our bodies.

Molecular Dynamic simulations

Computer simulations that model the movement of atoms and molecules over time.

Molecular Dynamic simulations are used to study how molecules move and interact. They can help scientists understand how proteins work, how drugs bind to targets, and more.