RESEARCH: CANCER
FOLDING PROJECT #15307 PROFILE

This project looks at graspetides, which are special chemicals made by bacteria. These chemicals have a ring shape that makes them strong and useful for fighting infections or blocking enzymes. Scientists will use computer simulations to figure out how these rings form during the creation process 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 with macrolactam or macrolactone linkages.

Graspetides are a special type of peptide created by living organisms. They have a unique ring structure that makes them strong and useful for various purposes like fighting infections, stopping viruses, and inhibiting enzymes. Scientists are trying to understand how these rings are formed and what makes each group of graspetides different.

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RiPPs

Ribosomally synthesized and post-translationally modified peptides

RiPPs are short chains of amino acids produced by ribosomes (protein factories) in cells. They undergo further modifications after creation to become functional molecules with diverse roles like antibiotics or signaling agents.

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ATP-grasp ligase

An enzyme that uses ATP to catalyze the formation of peptide bonds.

ATP-grasp ligases are proteins that act like molecular glue, using energy from ATP (cellular energy currency) to join amino acids together and build larger peptides. They play a crucial role in creating specific types of peptides, including graspetides.

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Macrolactam

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

Macrolactam is a special type of ring structure found in some peptides. It's created when an amino group (NH2) reacts with a carboxylic acid group (COOH), forming a stable ring that increases the peptide's stability and helps it perform its functions.

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Macrolactone

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

Macrolactone is another type of ring structure found in some peptides. It's created when an alcohol group (OH) reacts with a carboxylic acid group (COOH), forming a stable ring that increases the peptide's stability and helps it perform its functions.

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Molecular dynamics (MD)

A computer simulation method used to model the movement of atoms and molecules over time.

Molecular dynamics (MD) is like a virtual microscope that lets scientists see how molecules move and interact at the atomic level. It uses computer simulations to track the movements of atoms in a molecule, providing insights into how they fold, bind to other molecules, and carry out their functions.