RESEARCH: HALOGENASES
FOLDING PROJECT #19214 PROFILE

Many medicines use halogens (like fluorine or chlorine). Adding these can be tricky and make harmful stuff. Scientists are studying enzymes called halogenases to make this process safer and more precise. This project uses computer models to predict where halogenases will add halogens to different molecules.

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

Approximately 40 percent of drugs approved or currently in clinical testing contain halogens (F, Cl, Br, or I) as pharmaceutically active ligand substituents.

This makes the halogenation of chemical scaffolds an issue of particular interest to medicinal chemists when attempting to synthesize potential drug candidates.

Many of the current methods for halogenation are difficult to control the regioselectivity or produce toxic byproducts during the reaction.

Due to these issues; halogenases, a class of enzymes that catalyze highly regioselective halogenation of various molecules in nature, have been studied as a means to improve existing halogenation methods with less toxic byproducts and higher regioselectivity of reaction.

By utilizing Relative Binding Free Energy calculations (RBFE) across a number of common organic molecule scaffolds, our goal is to better predict the probability and site of halogenation for various common chemical scaffolds across a number of halogenases.

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halogen

Elements fluorine, chlorine, bromine, or iodine.

Halogens are a group of highly reactive elements often used in pharmaceuticals due to their ability to modify drug properties. They can enhance solubility, target specific tissues, and influence drug activity.

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pharmaceutically active ligand

A molecule that binds to a specific target (e.g., receptor, enzyme) and produces a pharmacological effect.

Pharmaceutically active ligands are the core components of medications. They interact with biological targets to exert therapeutic effects.

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regioselectivity

The preferential formation of one isomer over others during a chemical reaction.

Regioselectivity refers to the ability of a chemical reaction to produce a specific isomer (molecule with the same atoms arranged differently). This is crucial in drug synthesis for ensuring the desired biological activity.

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halogenases

Enzymes that catalyze the regioselective halogenation of organic molecules.

Halogenases are enzymes found in nature that introduce halogens (fluorine, chlorine, bromine, iodine) into organic molecules. They are highly efficient and selective, making them valuable tools for drug development.

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Relative Binding Free Energy calculations (RBFE)

RBFE

RBFE calculations are used in drug discovery to predict the binding affinity of potential drug candidates to their target molecules. They provide valuable insights into the interactions between drugs and biological targets.