RESEARCH: HALOGENASES
FOLDING PROJECT #19203 PROFILE

Many new drugs use halogens (like chlorine or fluorine). Adding these can be tricky for scientists. The project relates to using computer models to predict where enzymes called 'halogenases' will add halogens to molecules, making drug development easier and safer.

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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halogens

Elements fluorine (F), chlorine (Cl), bromine (Br), and iodine (I).

Halogens are chemical elements that include fluorine, chlorine, bromine, and iodine. They are frequently used in drug development as they can influence a molecule's properties and interactions with biological targets.

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pharmaceutically

Relating to the preparation, dispensing, or use of drugs.

This word refers to anything related to the creation, distribution, or application of medicines. It's a key concept in pharmacology and drug development.

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ligand

A molecule that binds to a receptor or enzyme.

Ligands are molecules that attach to specific receptors or enzymes in the body. They can trigger various biological responses, making them crucial for drug action.

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scaffold

A basic structural framework for a molecule.

In chemistry, a scaffold is the core structure of a molecule. Medicinal chemists often use scaffolds as starting points to design new drugs.

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regioselectivity

The preference of a reaction to form one product over others based on position.

Regioselectivity describes how a chemical reaction favors the formation of one specific product over others, depending on where the reaction occurs within a molecule.

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halogenases

Enzymes that catalyze halogenation reactions.

Halogenases are specialized enzymes found in nature that facilitate the addition of halogens (like fluorine or chlorine) to other molecules.

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Relative Binding Free Energy calculations

RBFE

Relative Binding Free Energy calculations (RBFE) are a computational method used to predict the strength of binding between a molecule and a target (like a protein). This helps in designing new drugs.