Molecular mechanisms of spectral tuning and excited-state decay in phytochrome photoreceptors

Most organisms on earth are able to sense light, to which they adapt their behavior by using photoreceptor proteins containing light-absorbing chromophores. Phytochrome photoreceptors contain a covalently-attached tetrapyrrole chromophore and switch between two thermally stable forms, a red-absorbing (Pr) and a far-red-absorbing (Pfr) state. Although phytochromes have been studied for more than fifty years, the molecular mechanisms defining their photoinduced properties are not fully understood, hampering the efficient engineering of phytochrome-based molecular tools. The computational study presented in this thesis combines quantum chemical calculations and molecular dynamics simulations in order to elucidate the molecular mechanisms of spectral tuning and excited-state decay in phytochromes. The calculations have demonstrated that the spectral red shift of the Pfr state is induced by the hydrogen bond formation between the chromophore and a highly conserved aspartate. Here it is also shown how the formation of this hydrogen bond is coupled to dynamics of other active-site interactions. In addition, the chromophore deprotonation by a protein residue is proposed to contribute to the absorption at the Q-band blue shoulder in the Pr-state spectrum. For the first time, the photoinduced electron transfer coupled to proton transfer was characterized in phytochromes. These charge transfer pathways may contribute to the excited-state decay by quenching fluorescence and influencing photoproduct formation. The discoveries provided in this thesis will facilitate further phytochrome investigations and the rational design of phytochrome-based fluorescent markers and optogenetic tools

A Hydrogen Bond Between Linear Tetrapyrrole and Conserved Aspartate Causes the Far-Red Shifted Absorption of Phytochrome Photoreceptors

Photoswitching of phytochrome photoreceptors between red-absorbing (Pr) and far-red absorbing (Pfr) states triggers light adaptation of plants, bacteria and other organisms. Using quantum chemistry, we elucidate the color-tuning mechanism of phytochromes and identify the origin of the Pfr-state red-shifted spectrum. Spectral variations are explained by resonance interactions of the protonated linear tetrapyrrole chromophore. In particular, hydrogen bonding of pyrrole ring D with the strictly conserved aspartate shifts the positive charge towards ring D thereby inducing the red spectral shift. Our MD simulations demonstrate that formation of the ring D–aspartate hydrogen bond depends on interactions between the chromophore binding domain (CBD) and phytochrome specific domain (PHY). Our study guides rational engineering of fluorescent phytochromes with a far-red shifted spectrum

A Hydrogen Bond Between Linear Tetrapyrrole and Conserved Aspartate Causes the Far-Red Shifted Absorption of Phytochrome Photoreceptors

Photoswitching of phytochrome photoreceptors between red-absorbing (Pr) and far-red absorbing (Pfr) states triggers light adaptation of plants, bacteria and other organisms. Using quantum chemistry, we elucidate the color-tuning mechanism of phytochromes and identify the origin of the Pfr-state red-shifted spectrum. Spectral variations are explained by resonance interactions of the protonated linear tetrapyrrole chromophore. In particular, hydrogen bonding of pyrrole ring D with the strictly conserved aspartate shifts the positive charge towards ring D thereby inducing the red spectral shift. Our MD simulations demonstrate that formation of the ring D–aspartate hydrogen bond depends on interactions between the chromophore binding domain (CBD) and phytochrome specific domain (PHY). Our study guides rational engineering of fluorescent phytochromes with a far-red shifted spectrum.</jats:p

Zeo-1 : a computational data set of zeolite structures

Fast, empirical potentials are gaining increased popularity in the computational fields of materials science, physics and chemistry. With it, there is a rising demand for high-quality reference data for the training and validation of such models. In contrast to research that is mainly focused on small organic molecules, this work presents a data set of geometry-optimized bulk phase zeolite structures. Covering a majority of framework types from the Database of Zeolite Structures, this set includes over thirty thousand geometries. Calculated properties include system energies, nuclear gradients and stress tensors at each point, making the data suitable for model development, validation or referencing applications focused on periodic silica systems

Improving the silicon interactions of GFN-xTB

A general-purpose density functional tight binding method, the GFN-xTB model is gaining increased popularity in accurate simulations that are out of scope for conventional ab initio formalisms. We show that in its original GFN1-xTB parametrization, organosilicon compounds are described poorly. This issue is addressed by re-fitting the model's silicon parameters to a data set of 10 000 reference compounds, geometry-optimized with the revPBE functional. The resulting GFN1(Si)-xTB parametrization shows improved accuracy in the prediction of system energies, nuclear forces, and geometries and should be considered for all applications of the GFN-xTB Hamiltonian to systems that contain silicon