RESEARCH: CANCER
FOLDING PROJECT #18911 PROFILE

Lasso peptides are unique proteins with a knot-like structure that makes them super strong and good at binding to targets. Scientists want to understand how lasso peptides fold into this shape using computer simulations. The project relates to figuring out the steps involved in lasso peptide folding so we can make them even stronger and easier to produce.

Lasso peptides are a class of RiPPs that are found in bacteria and characterized by a specific knotted structure, called lasso fold.

They have a macrolactam ring formed between the N-terminus and a glutamate or aspartate at position 8 or 9.

The C-terminal tail is trapped within the macrocycle.

This knotted structure confers lasso peptide remarkable thermal and proteolytic stability.

Furthermore, the specific shape and volume enable these peptides to bind important receptors, which cannot be easily targeted by traditional antibodies and small molecule drugs.

Lasso peptides have been promosing drug candidates for treating human diseases such as cancer and autoimmune disorders.

Elucidating the folding process of lasso peptide and finding the key features regulating the formation of the lasso topology will allow us to enhance their stability and facilate its formation by lasso synthetases.

However, how lasso peptides fold into this lariat knot structure is still unclear.

In this study, we would like to run atomic-level MD simulation for each of 20 lasso peptides with known structures.

Lasso peptide

A class of peptides with a knotted structure.

Lasso peptides are a unique type of peptide found in bacteria. They have a distinctive 'knotted' shape, called the lasso fold, which makes them very stable and resistant to breaking down. This unique structure allows them to bind to specific targets in cells, making them promising candidates for new drugs to treat diseases like cancer and autoimmune disorders.

RiPPs

Ribosomally synthesized and post-translationally modified peptides

RiPPs are a diverse group of peptides produced by bacteria. They are initially made by ribosomes, but then undergo further chemical modifications after they are produced. These modifications give RiPPs their unique properties and functions.

Macrolactam

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

A macrolactam is a type of ring structure that forms when a carboxylic acid group reacts with an amine group. These rings are often found in natural products and pharmaceuticals because they can contribute to stability and specific binding properties.

MD simulation

A computer simulation of the motion of atoms and molecules over time.

MD simulations are used to study how molecules move and interact. This can help researchers understand the structure and function of proteins, design new drugs, and predict how materials will behave.