RESEARCH: CANCER
FOLDING PROJECT #15303 PROFILE

Lanthipeptides are powerful natural chemicals that can fight diseases. ProcM is a special enzyme that makes them, but scientists don't know exactly how it chooses where to act. This project uses computer simulations to understand how ProcM works at the atomic level, hoping to unlock its secrets for creating new medicines.

Note: This TLDR is a simplication and may not be 100% accurate.

Lanthipeptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) produced from precursor peptides through dehydration and cyclization reactions.

They exhibit a broad range of bioactivities, including anticancer, antimicrobial, antiviral, and antiallodynic effects.

ProcM, a class II lanthipeptide synthetase, is notable for its high substrate tolerance.

Remarkably, this single enzyme can catalyze the cyclization of a diverse array of substrates with high fidelity—an ability that has been extensively leveraged in the bioengineering of novel lanthipeptides.

Despite this, the molecular mechanism by which ProcM determines the site-selectivity of its substrates remains unclear.

In this study, we aim to perform atomic-level molecular dynamics (MD) simulations of the wild-type (WT) and Variant ProcM–ProcA3.3 complexes to investigate the basis of ProcM's site-selectivity.

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Lanthipeptides

A class of ribosomally synthesized peptides with post-translational modifications.

Lanthipeptides are a type of antimicrobial peptide produced by bacteria. They have a unique structure characterized by the presence of dehydrated amino acids and rings formed through cyclization reactions. Lanthipeptides exhibit various biological activities, including antibacterial, antiviral, and anticancer properties.

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RiPPs

Ribosomally Synthesized and Post-translationally Modified Peptides

RiPPs are a class of peptides synthesized by ribosomes and further modified after their production. These modifications often include dehydration and cyclization reactions, leading to unique structural features that contribute to their biological activity.

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ProcM

A class II lanthipeptide synthetase enzyme.

ProcM is an enzyme involved in the biosynthesis of lanthipeptides. It catalyzes the cyclization reaction that forms the characteristic rings in these peptides. ProcM exhibits high substrate tolerance, meaning it can process a wide variety of precursor peptides.

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Molecular Dynamics (MD)

Computational method for simulating the movement of atoms and molecules over time.

Molecular dynamics simulations are used to study the behavior of biological molecules like proteins. By simulating their movement and interactions, researchers can gain insights into how these molecules function at the atomic level.

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Wild-type (WT)

Refers to the naturally occurring form of a gene or protein.

Wild-type refers to the original, unmodified form of a gene or protein. It serves as a baseline for comparison when studying mutations or variations in these molecules.

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Variant

A modified form of a gene or protein.

A variant is a different version of a gene or protein compared to the wild-type. These variations can arise from mutations or deliberate genetic modifications.