RESEARCH: CANCER
FOLDING PROJECT #18912 PROFILE

Lasso peptides are special bacterial proteins with a unique knot-like shape that makes them very stable. Scientists want to understand how they fold into this shape using computer simulations. This project will simulate the folding of 20 different lasso peptides to learn more about their structure and potential uses as drugs.

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 antimicrobial peptides with a knotted structure

Lasso peptides are a unique type of antibiotic produced by bacteria. They have a distinctive knot-like shape that makes them very stable and able to bind strongly to specific targets. This makes 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 large and diverse group of peptides produced by bacteria. They are made in ribosomes, like other proteins, but then undergo further modifications after production. These modifications can include the addition of chemical groups or the formation of unusual structures, giving RiPPs their unique properties.

Macrolactam ring

A large cyclic structure formed by a peptide bond between the N-terminus and C-terminus

A macrolactam ring is a type of chemical structure found in some peptides. It's formed when the end of a peptide chain (the N-terminus) connects to another part of the same chain (the C-terminus), creating a large ring. This structure contributes to the stability and unique properties of lasso peptides.

MD simulation

A computational method used to simulate the movement of atoms and molecules over time

MD simulation is a powerful tool used by scientists to study how molecules behave. It involves using computers to model the interactions between atoms and molecules, allowing researchers to see how they move, interact, and change shape over time.

Atomic-level

Describing the level of detail at which individual atoms are considered

Atomic-level refers to the scale at which we are looking at molecules. In this context, it means that the simulation will consider the movement and interactions of each individual atom within the lasso peptides.