New advance in computational chemistry: full quantummechanical ab initio computation of streptavidin-biotin interaction energy

Benchmark full quantum mechanical Hartree-Fock calculation has been carried out to compute interaction energies for the streptavidin-biotin binding complex. In this report, the entire streptavidin-biotin interaction system with a total of 1775 atoms is treated by quantum mechanics. The full quantum energy calculation for this protein system is made possible by applying a recently developed MFCC approach in which the protein molecule is decomposed into amino-acid-based fragments that are properly capped. Ab initio calculations are performed at the Hartree-Fock level with a 3-21G basis set. The energies are computed for geometries of the binding complex near two configurations, corresponding to the crystal structure of the binding complex and a minimum energy geometry found from molecular force field, respectively. Comparisons are made of the computed ab initio energies with those from a force field. The present calculation shows that ab initio binding energies (at HF/3-21G level) are almost 30 kcal/mol larger than those given by a force field. Fully quantum mechanical computation of protein interaction energy presents a grand challenge to computational chemists. The large size of proteins with thousands of atoms makes it impractical to attempt brute force ab initio calculations using standard quantum chemistry methods. Standard applications o