Benchmark Study of the SCC-DFTB Approach for a Biomolecular Proton Channel

The self-consistent charge density functional tight binding (SCC-DFTB) method has been increasingly applied to study proton transport (PT) in biological environments. However, recent studies revealing some significant limitations of SCC-DFTB for proton and hydroxide solvation and transport in bulk aqueous systems call into question its accuracy for simulating PT in biological systems. The current work benchmarks the SCC-DFTB/MM method against more accurate DFT/MM by simulating PT in a synthetic leucine–serine channel (LS2), which emulates the structure and function of biomolecular proton channels. It is observed that SCC-DFTB/MM produces overcoordinated and less structured pore water, an overcoordinated excess proton, weak hydrogen bonds around the excess proton charge defect, and qualitatively different PT dynamics. Similar issues are demonstrated for PT in a carbon nanotube, indicating that the inaccuracies found for SCC-DFTB are not due to the point charge based QM/MM electrostatic coupling scheme, but rather to the approximations of the semiempirical method itself. The results presented in this work highlight the limitations of the present form of the SCC-DFTB/MM approach for simulating PT processes in biological protein or channel-like environments, while providing benchmark results that may lead to an improvement of the underlying method.