RESEARCH: CANCER
FOLDING PROJECT #18924 PROFILE

This project studies lasso peptides, tiny proteins with a unique shape that could be used to make new drugs. Scientists aren't sure exactly how these peptides form their shape, so this research will use computer simulations to understand the process and discover how lasso peptides are made.

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

Ribosomally synthesized and post-translationally modified peptide natural products.

Lasso peptides are a unique type of natural product produced by ribosomes. They have a distinctive loop structure and show promise as potential drugs due to their anticancer, antibacterial, and antiviral properties.

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Ribosomally synthesized

Produced by ribosomes.

Ribosomes are cellular structures responsible for protein synthesis. When a molecule is 'ribosomally synthesized', it means it was created using the machinery of ribosomes.

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Post-translationally modified

Modified after protein synthesis.

Proteins often undergo modifications after they are created by ribosomes. These changes can alter a protein's function, location, or interactions with other molecules.

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RiPP

Ribosomally produced peptides

RiPP stands for Ribosomally Produced Peptides. These are a special class of naturally occurring molecules that are made by ribosomes and have diverse biological activities.

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Macrolactam ring

A large cyclic amide structure.

A macrolactam ring is a large, ring-shaped molecule containing an amide bond. In lasso peptides, this ring forms a crucial part of their unique structure.

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Lasso peptide cyclase

An enzyme that catalyzes the formation of lasso peptide macrolactam ring.

Lasso peptide cyclase is a specialized enzyme that plays a key role in creating the unique loop structure of lasso peptides. It facilitates the formation of the macrolactam ring by joining specific parts of the peptide chain.

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Molecular Dynamic simulations

Computer simulations of molecular movement and interactions.

Molecular Dynamic simulations are powerful tools used in computational biology to study the behavior of molecules over time. They involve simulating the movements and interactions of atoms and molecules to understand their structure and function.