RESEARCH: CANCER
FOLDING PROJECT #15310 PROFILE

This project looks at how tiny proteins called graspetides fold into shapes that give them special powers like fighting viruses and bacteria. Using computer simulations, scientists will compare how different types of graspetides fold to understand the rules behind their unique structures.

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 special type of peptide produced by living organisms. They have unique ring structures that make them strong and able to perform many different tasks, 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 being made, they undergo further modifications to become active.

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ATP-grasp ligase

An enzyme that uses ATP to form chemical bonds.

ATP-grasp ligases are a type of enzyme that uses energy from ATP to join molecules together.

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Macrolactam

A type of cyclic amide.

Macrolactam is a ring-shaped molecule containing an amide bond. They are found in some peptides and give them stability.

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Macrolactone

A type of cyclic ester.

Macrolactone is a ring-shaped molecule containing an ester bond. They are found in some peptides and give them stability.

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Antimicrobial

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

Antimicrobial refers to substances that can fight against infections caused by bacteria, viruses, fungi, or parasites.

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Antiviral

Having the ability to inhibit the replication of viruses.

Antiviral refers to substances that can stop or slow down the growth and spread of viruses.

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Enzyme inhibitory

Having the ability to inhibit the activity of enzymes.

Enzyme inhibitors are molecules that can block or slow down the action of enzymes. They are often used in drugs to treat various diseases.

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Molecular dynamics (MD)

Molecular dynamics

MD simulations are computer models that track the movement of atoms and molecules over time. This helps scientists understand how proteins fold and interact.

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Folding trajectories

The path that a molecule takes as it folds into its final shape.

Folding trajectories show the step-by-step process of how a protein or other molecule folds into its correct three-dimensional structure.