Direct Observation of CH/CH van der Waals Interactions in Proteins by NMR

van der Waals interactions are important to protein stability and function. These interactions are usually identified empirically based on protein 3D structures. In this work, we performed a solution nuclear magnetic resonance (NMR) spectroscopy study of van der Waals interactions by detecting the through-space vdw JCC-coupling between protein aliphatic side chain groups. Specifically, vdw JCC-coupling values up to ∼0.5 Hz were obtained between the methyl and nearby aliphatic groups in protein GB3, providing direct experimental evidence for the van der Waals interactions. Quantum mechanical calculations suggest that the J-coupling is correlated with the exchange-repulsion term of van der Waals interaction. NMR detection of vdw JCC-coupling offers a new tool to characterize such interactions in proteins.