Molecular Mechanics for Transition Metal Centers: From Coordination Complexes To Metalloproteins

Abstract

Abstract Computer modeling of transition metal centers presents many challenges. Whether in relatively small complexes or attached to large biomolecules, the electronic structure arising from the open-shell d n configuration can be complicated. Most workers therefore resort to quantum mechanical (QM) methods, notably density functional theory (DFT). However, many problems require large numbers of calculations: e.g., high-throughput screening, comprehensive conformational searching, and molecular dynamics. In these cases, all forms of QM, including DFT, are prohibitively expensive and impractical. In contrast, classical molecular mechanics (MM) is fast enough and has for many years been used for such large-scale computations. Unfortunately, while MM works well for “organic” systems, it is not well suited to TM systems since it misses many important d-electron effects which are implicit in QM methods. However, since we cannot make QM methods much faster, the only option is to make MM smarter. We have combined ligand field theory (LFT), in its angular overlap model (AOM) form, with “normal” MM to give ligand field molecular mechanics (LFMM). LFMM has a sophisticated AOM description of metal–ligand bonding which can be designed to emulate DFT. However, since LFT is empirical, LFMM is up to four orders of magnitude faster than DFT. Illustrative applications are presented which span the structural chemistry of Ga(III) and Mn(II) complexes, Jahn–Teller effects in Cu(II) and Fe(II) systems, the trans -influence in Pt(II) chemistry, spin-state changes in Ni(II) and Co(III) species, transition states for water exchange at first-row M(II) centers, through to 16 ns molecular dynamics simulations of copper proteins. Provided the necessary investment in parameter development is justifiable, LFMM provides DFT-like accuracy at a MM cost and represents a powerful, general tool for modeling TM centers in coordination complexes and metalloproteins.