RESEARCH: CANCER
FOLDING PROJECT #15306 PROFILE

This project relates to graspetides, which are small proteins with special rings that give them different abilities 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 rings.

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 (RiPPs)

Graspetides are a type of peptide produced by living organisms. They have unique structural features called macrolactam or macrolactone linkages that make them stable and effective against things like bacteria, viruses, and enzymes. Researchers are studying how graspetides are made and how their structure influences their activity.

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RiPPs

Ribosomally synthesized and post-translationally modified peptides

RiPPs stand for ribosomally synthesized and post-translationally modified peptides. They are a diverse group of bioactive compounds produced by bacteria, fungi, and plants. RiPPs have various applications in medicine, agriculture, and biotechnology.

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ATP-grasp ligase

An enzyme that catalyzes the formation of macrolactam or macrolactone linkages

ATP-grasp ligases are a type of enzyme involved in making special chemical bonds in peptides. They use energy from ATP to create macrocyclic structures, which are rings found in many bioactive molecules.

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Macrolactam

A cyclic amide formed by the reaction of an amine with a carboxylic acid

Macrolactam is a type of ring structure found in some peptides. It's formed when an amine group reacts with a carboxylic acid group, creating a stable loop-like shape.

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Macrolactone

A cyclic ester formed by the reaction of an alcohol with a carboxylic acid

Macrolactone is another type of ring structure found in some peptides. It's formed when an alcohol group reacts with a carboxylic acid group, creating a stable loop-like shape.

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Molecular Dynamics (MD)

A computer simulation technique used to study the motion of atoms and molecules over time

Molecular Dynamics (MD) is a powerful tool used by scientists to simulate how molecules move and interact. By running these simulations on computers, researchers can gain insights into complex biological processes.

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Folding Trajectories

The path followed by a molecule as it folds into its final three-dimensional structure

Folding trajectories describe the step-by-step process by which a molecule, like a protein, changes shape to become functional. Scientists use these trajectories to understand how proteins fold and what influences their shape.