Applications of Density Functional Theory to Biological Systems

Abstract

The term biological systems may be used in reference to a wide class of polyatomic systems. They can be defined as minimal functional units which perform specific biological functions: enzymatic reactions, transport across membranes, or photosynthesis. At present, such systems as a whole are not amenable to quantum-chemistry studies because of their large size. The smallest enzymes are built of few thousands of atoms (e.g., lysozyme consists of 129 amino-acid subunits), the smallest nucleic acids are of similar size (e.g., t-RNA molecules consist of about 80 nucleotide subunits), whereas biological membranes are even larger and include different biological macromolecules embedded in a phospholipide medium. On the other hand, a common-sense definition of the term biological systems refers to any chemical molecule or molecular complex which is involved in biological or biochemical processes. The latter definition, which will be used throughout this review, covers not only complete functional units performing biological functions but also fragments of such units. Theoretical studies have provided data on properties of such fragments and have helped understanding of the biological processes at the molecular level. Depending upon the size of such fragments, they can be studied by means of various quantum-chemical methods. Molecular systems of up to a few thousands of atoms can be studied using semi-empirical methods. For the Hartree-Fock or Kohn-Sham density functional theory (DFT) calculations, the current size limit is a few hundreds of atoms. (Throughout the text, Hartree-Fock refers to ab initio Self-Consistent Field calculations using the approximation of linear combination of atomic orbitals.) When the desired accuracy requires the calculation of electron correlation at the ab initio level, only systems containing no more than few tens of atoms can be treated. Therefore, a theoretician aiming at the elucidation of biological processes by quantum-mechanical calculations faces two crucial issues. The first one is the selection of a fragment for modeling at the quantum-mechanical level. The second one is the assessment of the effects associated with parts of the system which cannot be modeled at the quantum-mechanical level. In this review, the DFT studies of biological systems are divided into two groups corresponding to different ways of addressing the second aforementioned issue.