An approximate DFT method for QM/MM simulations of biological structures and processes

In the last years, we have developed a computationally efficient approximation to density functional theory, the so called self-consistent charge density functional tight-binding scheme (SCC-DFTB). To extend its applicability to biomolecular structures, this method has been implemented into quantum mechanical/molecular mechanics (QM/MM) and linear scaling schemes and augmented with an empirical treatment of the dispersion forces. We review here applications of the SCC-DFTB QM/MM method to proton transfer (PT) reactions in enzymes like liver alcohol dehydrogenase and triosephosphate isomerase. The computational speed of SCC-DFTB allows not only to compute minimum energy pathways for the PT but also the potential of mean force. Further applications concern the dynamics of polypeptides in solution and of ligands in their biological environment. The developments reviewed allowed for the first time realistic QM simulations of polypeptides, a protein and a DNA dodecamer in the nanosecond time scale.

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