Lee G. Pedersen

We investigated the possibility of inter-residue communication of side chains in barstar, an 89 residue protein, using mutual information theory. The normalized mutual information (NMI) of the dihedral angles of the side chains was obtained from all-atom molecular dynamics simulations. The accumulated NMI from an explicit solvent equilibrated trajectory (600 ns) with free backbone exhibits a parabola-shaped distribution over the inter-residue distances (0–36 Å): smaller at the end regimes but larger in the middle regime. This analysis, plus several other measures, does not find unusual long-range communication for free backbone in explicit solvent simulations. Proteins 2014; 82:2896–2901.

We investigate the dinuclear manganese, Mn(II)–Mn(II), active site of human cytosolic X-propyl aminopeptidase (XPNPEP1) by employing the QM/MM method. The optimized structure supports two manganese atoms at the active site and excludes the possibility of a single Mn(II) atom or another combination of divalent metal ions, Ca(II), Fe(II), an Mg(II). A broken-symmetry solution verifies an antiferromagnetically coupled state between the Mn(II)–Mn(II) pair, which is the ground state. From the energy difference between the high spin state (HS) and the broken-symmetry state (BS), we estimate the exchange coupling constant, J, to be 5.15 cm^–1. Also, we observe multiple bridges (p orbitals) from the solvent and two carboxylates linking to the Mn(II)–Mn(II), which leads to the weakly antiferromagnetic interaction of d⁵–d⁵ electrons through superexchange coupling.

Nature at the lab level in biology and chemistry can be described by the application of quantum mechanics. In many cases, a reasonable approximation to quantum mechanics is classical mechanics realized through Newton’s equations of motion. Dr. Pedersen began his career using quantum mechanics to describe the properties of small molecular complexes that could serve as models for biochemical systems. To describe large molecular systems required a drop-back to classical means and this led surprisingly to a major improvement in the classical treatment of electrostatics for all molecules, not just biological molecules. Recent work has involved the application of quantum mechanics for the putative active sites of enzymes to gain greater insight into the key steps in enzyme catalysis.