RESEARCH: CANCER
FOLDING PROJECT #15320 PROFILE

This project explores how graspetides, a type of naturally occurring protein, fold into unique shapes. By using computer simulations, researchers will try to understand the rules that govern how these proteins form their characteristic rings and if different types of graspetides have specific ways of folding.

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) characterized by macrolactam or macrolactone linkages.

Graspetides are a unique type of molecule produced by living organisms. They're made up of smaller building blocks called amino acids, linked together in specific patterns. These patterns create rings that give graspetides their strength and allow them to perform various functions like fighting infections or blocking the activity of enzymes.

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Ribosomally synthesized and post-translationally modified peptides (RiPPs)

Ribosomally synthesized and post-translationally modified peptides (RiPPs)

This refers to a group of molecules made by ribosomes within cells. They are initially produced as simpler chains that then undergo chemical changes after they are created. These modifications often turn them into potent drugs or tools used in research.

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Macrolactam

A cyclic amide formed by the reaction between an amino group and a carboxyl group in a molecule.

Think of macrolactams as large rings formed by chemical connections within a molecule. These rings often give molecules extra strength and stability.

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Macrolactone

A cyclic ester formed by the reaction between a hydroxyl group and a carboxyl group in a molecule.

Macrolactones are similar to macrolactams but instead of an amide bond, they have an ester bond. They also form rings within molecules, providing stability.

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Molecular Dynamics (MD) Simulations

Molecular Dynamics (MD) Simulations

This involves using powerful computers to model how atoms and molecules move and interact over time. It's a way to understand how molecules behave without having to do physical experiments.