Fluorine in protein environments: a QM and MD study

Area of Science:

• Biochemistry and structural biology
• Computational chemistry and molecular modeling

Background:

• Noncanonical amino acids with novel side chains improve peptide and protein properties.
• Fluorinated amino acids are increasingly vital in protein engineering, yet their behavior in protein environments requires further elucidation.

Purpose of the Study:

• To characterize the physicochemical properties of fluorinated amino acids using quantum mechanics (QM) and molecular dynamics (MD) methods.
• To understand the fundamental properties of fluorine within protein environments for advanced protein engineering.

Main Methods:

• Analyzed geometry, charges, and hydrogen bonding of fluorinated ethane derivatives using QM.
• Parametrized four fluorinated L-amino acids for AMBER force field: MfeGly, DfeGly, TfeGly, DfpGly.
• Characterized molecular volumes, conformational preferences, and hydration properties of these amino acids.

Main Results:

• Fluorine and hydrogen atoms in fluoromethyl groups can act as weak hydrogen bond acceptors or donors.
• Hydration of fluorinated amino acids is more favorable than their nonfluorinated counterparts.
• Hydrophobicity increases with the number of fluorine atoms, correlating with experimental data.

Conclusions:

• Fluorine incorporation significantly impacts amino acid properties, including hydrogen bonding and hydrophobicity.
• This research provides crucial insights into fluorine's role in protein environments.
• Understanding these properties is key to leveraging fluorine for enhanced protein engineering and drug design.