RESEARCH: HALOGENASES
FOLDING PROJECT #19211 PROFILE

Many drugs use halogens (like fluorine). Adding these is tricky! Enzymes called halogenases do it naturally, and really well. This project uses computer models to predict how halogenases add halogens to different molecules, helping us design better drugs.

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 a group of highly reactive elements frequently used in pharmaceutical development. They can be attached to drug molecules to alter their properties, such as their effectiveness or how they are absorbed by the body.

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ligand

A molecule that binds to a specific target protein or receptor.

Ligands are molecules that attach to proteins or receptors in the body. They can activate or block these targets, leading to various biological effects. In drug development, ligands are often designed to interact with specific targets to produce therapeutic effects.

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medicinal chemists

Scientists specializing in designing and synthesizing new drug molecules.

Medicinal chemists are scientists who use their knowledge of chemistry and biology to design and create new drugs. They work to develop molecules that can target specific diseases or conditions.

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regioselectivity

The ability of a chemical reaction to preferentially form one specific isomer over others.

Regioselectivity refers to the preference of a chemical reaction to produce one specific product over others when multiple products are possible. This is important in drug synthesis because it ensures that the desired drug molecule is produced.

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halogenases

Enzymes that catalyze the addition of halogens to organic molecules.

Halogenases are a type of enzyme that helps organisms add halogen atoms (like fluorine, chlorine, bromine) to other molecules. This process is important for many biological functions and has potential applications in drug development.

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Relative Binding Free Energy calculations (RBFE)

A computational method used to predict the binding affinity of molecules to a target.

RBFE calculations are a computer-based technique used in drug development to estimate how strongly a molecule binds to its intended target. This information helps scientists design more effective drugs.