RESEARCH: CANCER
FOLDING PROJECT #15318 PROFILE

This project relates to graspetides, which are special molecules with unique rings that give them strong powers. Scientists will use computer simulations to figure out how these rings form and why different types of graspetides have different ring 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.

---

Graspetides

A class of ribosomally synthesized and post-translationally modified peptides with macrolactam or macrolactone linkages.

Graspetides are a unique type of peptide produced by living organisms. They have a specific structure characterized by rings formed through chemical reactions. These rings give them stability and allow them to have various biological activities, such as fighting infections or inhibiting enzymes.

---

Ribosomally synthesized

Process of protein synthesis occurring within ribosomes.

Ribosomally synthesized means that a protein was made using the cellular machinery called ribosomes. Ribosomes are responsible for translating genetic information into proteins.

---

Post-translationally modified

Chemical alterations to a protein after its initial synthesis.

Post-translationally modified means that changes were made to a protein *after* it was initially created by ribosomes. These modifications can alter the protein's function and properties.

---

RiPPs

Ribosomally synthesized and post-translationally modified peptides.

RiPPs are a broad class of peptides created by living organisms. They are unique because they undergo chemical modifications after being made by ribosomes.

---

ATP-grasp ligase

An enzyme that catalyzes the formation of macrolactam or macrolactone linkages.

ATP-grasp ligases are enzymes that help build specific ring structures in peptides. They use energy from ATP to create these rings.

---

Macrolactam

A cyclic amide formed by linking the carboxyl group of one amino acid to an amino group on another.

Macrolactam is a type of ring structure found in some peptides. It's formed when a specific part of one amino acid connects to another.

---

Macrolactone

A cyclic ester formed by linking the carboxyl group of one amino acid to an hydroxyl group on another.

Macrolactone is another type of ring structure found in some peptides. It's formed when a specific part of one amino acid connects to a different functional group.

---

Molecular dynamics (MD)

A computational method for simulating the movement and interactions of atoms and molecules.

Molecular dynamics simulations are computer models that let scientists see how atoms and molecules move and interact. This helps understand complex processes like protein folding.