  Recent years have seen vast improvements in the ability of rigorous
quantum-mechanical methods to treat systems of interest to molecular biology.
In this review article, we survey common computational methods used to study
such large, weakly bound systems, starting from classical simulations and
reaching to quantum chemistry and density functional theory. We sketch their
underlying frameworks and investigate their strengths and weaknesses when
applied to potentially large biomolecules. In particular, density functional
theory---a framework that can treat thousands of atoms on firm theoretical
ground---can now accurately describe systems dominated by weak van der Waals
interactions. This newfound ability has rekindled interest in using this
tried-and-true approach to investigate biological systems of real importance.
In this review, we focus on some new methods within density functional theory
that allow for accurate inclusion of the weak interactions that dominate
binding in biological macromolecules. Recent work utilizing these methods to
study biologically-relevant systems will be highlighted, and a vision for the
future of density functional theory within molecular biology will be discussed.
