Large-scale ab initio quantum chemical calculations on biological systems

In this Account we describe recent advances in two ab initio electronic str ucture methods, localized perturbation approaches and density functional th eory, that allow accurate calculations including electron correlation to be carried out for systems with hundreds of atoms. Application of these metho ds to large-scale modeling of biological systems is discussed. Localized pe rturbation methods are best suited to computation of conformational energet ics and nonbonded interactions: determination of the relative energetics of various conformations of the alanine tetrapetide is presented. Density fun ctional theory is the method of choice for studying reactive chemistry; inv estigations of the catalytic cycle of the enzyme methane monooxygenase are reviewed.