RESEARCH: CANCER
FOLDING PROJECT #15315 PROFILE

This project relates to studying graspetides, which are tiny, ring-shaped proteins with various uses like fighting infections. Scientists will use computer simulations to figure out how these rings form and if different types of graspetides have unique ways of building their structure.

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 model species from multiple graspetide groups using atomic-level molecular dynamics (MD) simulations.

By comparing folding trajectories across these representative systems, we aim to identify conserved and group-specific determinants of ring pattern formation, and to assess whether distinct biosynthetic groups exhibit preferences for particular ring closure orders.

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Graspetides

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

Graspetides are a special type of peptide produced by living organisms. They have unique structures with rings that make them very stable. These rings also give them different abilities, like fighting infections or blocking enzymes.

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Ribosomally synthesized and post-translationally modified peptides (RiPPs)

Ribosomally synthesized and post-translationally modified peptides.

RiPPs are a type of peptide made by ribosomes (the protein factories in cells). After they're made, they go through changes to become more specialized. These changes can make them useful for fighting infections or doing other jobs.

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ATP-grasp ligase

An enzyme that uses ATP to join molecules together.

ATP-grasp ligases are enzymes that help cells build larger molecules. They use energy from ATP (the cell's fuel) to connect smaller pieces together.

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Macrolactam

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

Macrolactam is a special kind of ring structure found in some peptides. It's made when two parts of the peptide join together to form a closed loop.

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Macrolactone

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

Macrolactone is another type of ring structure found in some peptides. It's made when two parts of the peptide join together to form a closed loop, but this time with an oxygen atom instead of nitrogen.

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Molecular dynamics (MD) simulations

Computer simulations that model the motion of atoms and molecules.

Molecular dynamics simulations are like computer games for scientists. They help us understand how molecules move and interact with each other.