Methyl•••Methyl Interactions in Proteins: Insights from Structural and Computational Studies

• DOI: 10.1021/acs.jcim.5c00401
• Publication Date: 2025-04-21T10:43:51Z
• Authors: Juhi Dutta; Akshay Kumar Sahu; Subhrakant Jena; Himansu S. Biswal

The low affinity of nonpolar groups for water gave birth to one the significant supramolecular forces known as hydrophobic interaction early 1937. While precise origins this phenomenon remain debated, role London dispersion in stabilizing complexes is well-established. This article presents a comprehensive investigation nature and strength CH3•••H3C (methyl-methyl) interactions within amino acid residues proteins, employing combination quantum mechanical calculations custom Python code. Analysis isolated mimetic dipeptide models reveals that these are weak, with energies ranging from -2.40 -6.94 kJ/mol. These primarily attributed forces, supplemented by minor electrostatic contribution. Even though cumulative effect such vital flexible enzymatic center drug-protein interactions. Although experimental characterization weak challenging, our computational studies, presented herein, suggest solution-phase 13C NMR recently developed gas-phase terahertz (THz) spectroscopy offer promising avenues obtaining spectroscopic signatures elucidating their molecular origin.