DFTB+ is a versatile community developed open source software package offering fast and efficient methods for carrying out atomistic quantum mechanical simulations. By implementing various methods approximating density functional theory (DFT), such as the density functional based tight binding (DFTB) and the extended tight binding method, it enables simulations of large systems and long timescales with reasonable accuracy while being considerably faster for typical simulations than the respective ab initio methods. Based on the DFTB framework, it additionally offers approximated versions of various DFT extensions including hybrid functionals, time dependent formalism for treating excited systems, electron transport using non-equilibrium Green’s functions, and many more. DFTB+ can be used as a user-friendly standalone application in addition to being embedded into other software packages as a library or acting as a calculation-server accessed by socket communication. We give an overview of the recently developed capabilities of the DFTB+ code, demonstrating with a few use case examples, discuss the strengths and weaknesses of the various features, and also discuss on-going developments and possible future perspectives.

The primary step in the mechanism by which migratory birds sense the Earth's magnetic field is thought to be the light-induced formation of long-lived magnetically sensitive radical pairs within cryptochrome flavoproteins located in the birds' retinas. Blue-light absorption by the non-covalently bound flavin chromophore triggers sequential electron transfers along a chain of four tryptophan residues toward the photoexcited flavin. The recently demonstrated ability to express cryptochrome 4a from the night-migratory European robin (Erithacus rubecula), ErCry4a, and to replace each of the tryptophan residues by a redox-inactive phenylalanine offers the prospect of exploring the roles of the four tryptophans. Here, we use ultrafast transient absorption spectroscopy to compare wild type ErCry4a and four mutants having a phenylalanine at different positions in the chain. We find that each of the three tryptophan residues closest to the flavin adds a distinct relaxation component (time constants: 0.5, 30, and 150 ps) in the transient absorption data. The dynamics of the mutant containing a phenylalanine at the fourth position, furthest from the flavin, are very similar to those of wild type ErCry4a, except for a reduced concentration of long-lived radical pairs. The experimental results are evaluated and discussed in the framework of real-time quantum mechanical/molecular mechanical electron transfer simulations based on the density functional-based tight binding approach. This comparison between simulation results and experimental measurements provides a detailed microscopic insight into the sequential electron transfers along the tryptophan chain. Our results offer a route to the study of spin transport and dynamical spin correlations in flavoprotein radical pairs.

Hybrid quantum mechanical/molecular mechanical (QM/MM) methods have become indispensable tools for the study of biomolecules. In this article, we briefly review the basic methodological details of QM/MM approaches and discuss their applications to various energy transduction problems in biomolecular machines, such as long-range proton transports, fast electron transfers, and mechanochemical coupling. We highlight the particular importance for these applications of balancing computational efficiency and accuracy. Using several recent examples, we illustrate the value and limitations of QM/MM methodologies for both ground and excited states, as well as strategies for calibrating them in specific applications. We conclude with brief comments on several areas that can benefit from further efforts to make QM/MM analyses more quantitative and applicable to increasingly complex biological problems.