The chemistry in a living cell is amazing and challenging, and with advances made in the wavefunction technology, the horizon is wide open for any scientific adventure. In this work we explore two interesting processes that take place in any living cell. The first is the process of bioactivation of acetate ion by converting to Acetyl-Coenzyme A (CH3CO-CoA), known to be the most common biological thioester, where coenzyme A (CoASH) is the thiol used in cells to activate the carboxylic acids. Thioesters are known to be more reactive than oxygen esters toward the addition of nitrogen and carbon nucleophiles in a nucleophilic addition-elimination reaction. We employ density functional theory (DFT) B3LYP method with aug-cc-pVTZ basis set and natural bond orbital (NBO) methods and analyses to investigate the structure-reactivity relationship in both esters and thioesters and explain the unusual reactivity thioesters have relative to esters. We produce quantum mechanical properties such as stabilization energies, interaction strength, overlap integral along with contour (2d), surface plots (3d) with overlap images for all orbitals, which explain the observed chemistry. Secondly, we present a quantum mechanics view for hydrogen bonding, which is the reason for the formation of a given protein structure and the stability of its structure. These fundamental biochemical questions remain fascinating and challenging problems because the physical bases of the forces that govern protein structure, stability and folding are still not well understood. We show the physical bases for such important phenomena in modern structure biology and life.

Computational chemistry study in a living cell: Physical origins for bioactivation of carboxylic acids and the hydrogen bonding

247th National Meeting (2014)

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