Characterization of diverse non-covalent interactions associated with protein acetylation

Protein acetylation has early emerged as a major posttranslational modification for histones and was recently found to be involved in a variety of biological events such as enzymatic activation and signal transduction. Traditional notion about the physicochemical effects associated with protein acetylation is mainly because of its presence capable of neutralizing positively charged protein system, while diverse non-covalent interactions arising from the acetylation are largely ignored and have never been investigated systematically. In the current work, we perform a comprehensive examination of the geometrical profile and energetic landscape of such acetylation-related non-covalent interactions in protein context by using a combination of high-level ab initio calculations, crystal structure survey, and hybrid mechanical/molecular mechanical analysis, on the basis of small model complexes and real protein systems. It is all coming together to suggest that the formation of complicated non-covalent networks around the acetylated site of protein is fundamentally important for stabilizing local structure, improving systemic rigidity, and even conducting more sophisticated biological functions such as switching enzymatic activity.