Effect of mutation on the stabilization energy of HIV-1 zinc fingers: a hybrid local self-consistent field/molecular mechanics investigation.

Metal-ligand interactions give rise to a wide variety of metal complexes with various physical properties and chemical behaviours and numerous practical applications. The ability of the zinc ion to enhance the structural stability of many proteins by electrostatic interactions or by co-ordination with surrounding amino acids makes it the most important metal ion found in biological systems. In this paper, we highlight the importance of non-covalent interaction established between a metal ion and its environment in stabilizing biomolecules. Specifically, we are interested in understanding the stabilization role of the zinc ion in a native and point-mutated zinc-activated site. We have adapted a new quantum mechanics/molecular mechanics (QM/MM) strategy to describe a large molecular system; it is referred to as the local self-consistent field/MM method. It involves the use of frozen doubly occupied strictly localized bonding orbitals to link the QM subsystem to the one treated at the MM level. The B3LYP method, combined with LanL2DZ and 6-311G basis sets, was used to describe the QM region that comprised the zinc ion and the lateral chains of the four co-ordinating amino acids. For the surroundings (the backbone), CHARMM27 force field was used to describe MM interactions. The influence of the basis set size on the quality of the structural parameters of the zinc-binding site and the effects of mutation on the structural stabilization energy are analysed and reported.