RESEARCH: CANCER
FOLDING PROJECT #15313 PROFILE

This project looks at how graspetides, special proteins, fold into complex shapes. Graspetides have different types of rings that give them unique abilities. Scientists will use computer simulations to figure out how the order of ring formation depends on the specific type of graspetide and its building blocks.

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 unique type of peptide created by living organisms. They have a special structure with rings that give them strength and allow them to do many important jobs like fighting off infections or stopping enzymes from working. Scientists are studying how these rings form to better understand how graspetides work.

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Ribosomally synthesized peptides (RiPPs)

RiPPs

Ribosomally synthesized peptides (RiPPs) are a diverse group of small proteins produced by ribosomes in living organisms. They often undergo further modifications after being made, giving them unique properties and functions.

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ATP-grasp ligase

An enzyme that uses ATP to form bonds between molecules.

ATP-grasp ligases are enzymes that play a crucial role in building complex molecules. They use the energy from ATP to join smaller pieces together, creating larger structures essential for many biological processes.

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Macrolactam

A cyclic amide formed from a reaction between an amine and a carboxylic acid.

Macrolactam is a type of ring structure found in some peptides. It's formed when two parts of a molecule, an amine and a carboxylic acid, link together to create a closed loop. This ring structure can make the peptide more stable and give it special properties.

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Macrolactone

A cyclic ester formed from a reaction between an alcohol and a carboxylic acid.

Macrolactone is another type of ring structure found in some peptides. It's formed when two parts of a molecule, an alcohol and a carboxylic acid, link together to create a closed loop. This ring structure can make the peptide more stable and give it special properties.

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Antimicrobial

Relating to the inhibition of microbial growth.

Antimicrobial refers to substances or agents that can kill or inhibit the growth of microorganisms like bacteria, fungi, and viruses. They are essential for treating infections and preventing their spread.

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Antiviral

Relating to the inhibition of viral replication.

Antiviral refers to substances or agents that can prevent or reduce the replication of viruses within a host. They are crucial for treating viral infections and managing their spread.

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Enzyme inhibitory

Relating to the inhibition of enzyme activity.

Enzyme inhibitory refers to substances or agents that can block or reduce the activity of enzymes. Enzymes are proteins that catalyze (speed up) chemical reactions in living organisms, so inhibiting their activity can have various effects.

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Molecular dynamics (MD)

MD

Molecular dynamics (MD) is a powerful computer simulation technique used to study the movement and interactions of atoms and molecules over time. It allows scientists to understand how biological systems work at a detailed level.