RESEARCH: CANCER
FOLDING PROJECT #15311 PROFILE

This project investigates how graspetides, a type of antibiotic molecule, fold into their unique shapes. By using computer simulations, researchers will explore how the building blocks and folding pathways determine the order in which rings form within these molecules. The goal is to understand if different types of graspetides have preferences for specific ring formation patterns.

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 peptides with macrocyclic structures.

Graspetides are a type of naturally occurring molecule made by bacteria. They have rings in their structure which give them special properties like fighting infections and blocking enzymes.

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Ribosomally Synthesized Peptides (RiPPs)

Ribosomally synthesized peptides (RiPPs) are a class of antimicrobial peptides produced by ribosomes.

RiPPs are small proteins made by ribosomes in bacteria. They are often used to fight off other microbes.

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Macrolactam

A cyclic amide with a large ring structure.

Macrolactam is a type of molecule with a large ring that contains both an amine group and a carbonyl group.

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Macrolactone

A cyclic ester with a large ring structure.

Macrolactone is a type of molecule with a large ring that contains both an ester group and an oxygen atom.

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ATP-grasp ligase

An enzyme that catalyzes the formation of macrocycles in peptides using ATP.

ATP-grasp ligase is an enzyme that helps make large rings in proteins using energy from ATP.

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Molecular Dynamics (MD) Simulations

Computer simulations that model the movement and interactions of atoms in molecules.

MD simulations are computer programs that can show how atoms in molecules move and interact over time.