RESEARCH: HALOGENASES
FOLDING PROJECT #19205 PROFILE

Lots of drugs use halogens (like chlorine or fluorine). Adding these can be tricky and make toxic waste. The project relates to using computer models to predict how enzymes called halogenases add halogens to molecules, which could lead to safer and more efficient drug development.

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 elements known for their reactivity. In pharmaceuticals, they are often used as substituents on drug molecules to modify their properties, such as solubility or activity.

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pharmaceutically active ligand substituents

Parts of a drug molecule that bind to specific targets (like proteins) and produce a desired effect.

Pharmaceutically active ligand substituents are the chemical groups within a drug molecule that are responsible for its biological activity. These groups interact with specific targets in the body, such as proteins or receptors, to produce the desired therapeutic effect.

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medicinal chemists

Scientists who specialize in designing and synthesizing new drug molecules.

Medicinal chemists play a crucial role in drug development by designing and synthesizing new chemical compounds that have the potential to treat diseases. They combine knowledge of chemistry, biology, and pharmacology to create molecules with specific properties and therapeutic effects.

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halogenation

The process of adding a halogen atom to a molecule.

Halogenation is a chemical reaction that involves the addition of a halogen atom (fluorine, chlorine, bromine, or iodine) to an organic molecule. It is widely used in various industries, including pharmaceuticals and chemical manufacturing, for synthesizing new compounds with desired properties.

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regioselectivity

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

Regioselectivity refers to the preference of a chemical reaction to produce a specific isomer (a molecule with the same atoms arranged in a different order) over other possible isomers. It is an important consideration in organic synthesis, as controlling regioselectivity can lead to the desired product being formed more efficiently.

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halogenases

Enzymes that catalyze the regiospecific halogenation of organic molecules.

Halogenases are a special class of enzymes that facilitate the precise addition of halogens (fluorine, chlorine, bromine, or iodine) to organic molecules. These enzymes play a crucial role in various biological processes and have potential applications in biotechnology for synthesizing valuable compounds.

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Relative Binding Free Energy calculations (RBFE)

RBFE

Relative Binding Free Energy calculations (RBFE) are a computational method used to predict the binding affinity between two molecules. This technique is widely employed in drug discovery and development to assess the interactions between potential drug candidates and their target proteins.