Dissociation energy estimation of insulins using all-electron density functional calculation

COMP 222

Toru Inaba, toru.inaba.ap@hitachi.com, Mechanical Engineering Research Laboratory, Advanced Simulation Center, Hitachi, Ltd, 832-2, Horiguchi, Hitachinaka, Ibaraki, 312-0034, Japan and Fumitoshi Sato, satofumi@fsis.iis.u-tokyo.ac.jp, Insititute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8505, Japan.
The dissociation energy from an insulin dimer to its two monomers was estimated by using the ProteinDF, which can calculate the canonical wavefunction of proteins using the Gaussian-based density functional method. The computational molecules were native insulin (Regular), and mutant insulins, i.e. two rapid-acting insulins (Lispro and Aspart) and a long-acting insulin (Glargine). Molecular dynamics calculations of these insulin dimers were performed, and the five structures were chosen during their equilibrium states. We then calculated the all-electron energies for each dimer and its monomers. The dissociation energy was simply estimated by subtracting the energy of the dimer from the total energy of the monomers. The average number of residues, atoms, electrons, and orbitals for the calculated insulin dimers was 102, 1600, 6200, and 9000, respectively. The calculated order of average dissociation energy was Lispro, Aspart, Regular, and Glargine. This result was reasonable and these studies will pave the way in the design of new theoretical medicines. We will describe the method and some of the calculated properties in this poster.