RESEARCH: CANCER
FOLDING PROJECT #15322 PROFILE

This project relates to understanding how graspetides, special molecules with unique rings, are made. Researchers will use computer simulations to see how the parts of graspetides interact and figure out the order in which the rings form. This could lead to new ways to make these useful molecules for medicine.

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

Graspetides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) characterized by the ATP-grasp ligase–catalyzed macrolactam or macrolactone linkages in their structure.

These macrocycles impart structural stability and diverse bioactivities, including antimicrobial, antiviral, and enzyme inhibitory effects.

Graspetides are classified into distinct groups based on sequence motifs, cyclization patterns, and biosynthetic machinery.

While each group exhibits characteristic ring topologies, the molecular basis by which core peptide sequence and folding pathways dictate the order of ring formation remains poorly understood. In this study, we will investigate the interactions between graspetide precursor peptides and their respective ATP-grasp ligases using atomic-level molecular dynamics (MD) simulations.

By comparing the folding trajectories of these systems under differing conditions, we aim to identify and assess patterns in ring closure preference.

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Graspetides

A class of ribosomally synthesized and post-translationally modified peptides.

Graspetides are a special type of protein made by bacteria. They have a ring shape that makes them strong and useful for fighting infections or blocking enzymes. Scientists want to learn more about how these rings are formed.

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RiPPs

Ribosomally Synthesized and Post-translationally Modified Peptides

RiPPs are proteins made by ribosomes, like regular proteins. But after they're made, they go through special changes that make them very strong and useful for things like fighting infections.

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ATP-grasp ligase

An enzyme that uses ATP to join molecules together.

ATP-grasp ligases are special enzymes that use energy from ATP to connect pieces of molecules. They're important for making many different kinds of molecules, including proteins.

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Macrolactam

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

Macrolactam is a type of ring structure made from joining amino acids. It's very strong and stable, making it useful in things like medications.

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Macrolactone

A cyclic ester formed by a reaction between an alcohol and a carboxylic acid.

Macrolactone is another type of ring structure made from joining molecules. It's also very strong and stable, making it useful in things like medications.

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Molecular Dynamics (MD)

A computer simulation method for modeling the motion of atoms and molecules.

Molecular Dynamics is a computer program that lets scientists see how tiny parts of molecules move and interact. It's very useful for understanding how things like drugs work.