RESEARCH: CANCER
FOLDING PROJECT #18922 PROFILE

Lasso peptides are unique molecules that fight cancer and infections. This project uses computer simulations to understand how lasso peptides are made, focusing on a special enzyme called lasso peptide cyclase. By studying this process, scientists hope to create new drugs based on lasso peptides.

Note: This TLDR is a simplication and may not be 100% accurate.

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.

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Lasso peptides

A class of ribosomally synthesized peptides with a unique lariat-like structure.

Lasso peptides are a special type of peptide (chains of amino acids) produced by bacteria. They have a distinctive loop shape and can be used to target cells in the body. Scientists are studying them because they may be helpful in developing new drugs.

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Ribosomally synthesized

Produced by ribosomes, the cellular machinery responsible for protein synthesis.

Ribosomally synthesized means that something is made by ribosomes, which are tiny parts of cells that build proteins. Proteins are essential building blocks for all living things.

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Post-translationally modified

Chemical alterations made to a protein after its synthesis.

Post-translationally modified means that changes are made to a protein *after* it has been created by the cell. These modifications can alter how the protein works and where it goes in the cell.

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RiPP

Ribosomally produced peptides

RiPP stands for ribosomally produced peptide. It refers to a type of molecule made by bacteria that can have useful properties for medicine or other applications.

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Natural products

Compounds derived from natural sources.

Natural products are substances found in nature, like plants or microbes. They often have interesting properties and can be used to develop new medicines.

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Anticancer

Having the ability to inhibit or destroy cancer cells.

Anticancer refers to substances that can fight against cancer. They work by stopping cancer cells from growing or destroying them altogether.

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Antibacterial

Having the ability to kill or inhibit the growth of bacteria.

Antibacterial describes substances that can stop bacteria from growing or eliminate them. They are used to treat bacterial infections.

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Antiviral

Having the ability to inhibit the replication of viruses.

Antiviral refers to substances that can stop viruses from multiplying. They are used to treat viral infections.

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Molecular Dynamic (MD) simulations

Computer-based models used to simulate the motion of molecules over time.

Molecular Dynamic simulations are computer programs that mimic how molecules move and interact. They help scientists understand how molecules behave in different environments and can be used to design new drugs or materials.

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Cyclization

The process of forming a ring structure.

Cyclization is like connecting two ends of a chain to make a circle. In biology, it's often used to create stable structures in proteins or other molecules.