Towards ab initio optical spectroscopy of bacterial light-harvesting complexes
The key events in the light reactions of natural photosynthesis are the capture of photons, transport of electronic excitations (excitons) and the separation of excitons into free charges. These processes are carried out in pigment-protein complexes (PPCs), in which optically active pigments, often chlorophyll derivatives, are spatially co-ordinated in a protein matrix. Remarkably, the molecular architecture and pigment-protein interactions in PPCs often allows 100% quantum efficiency for the conversion of a captured photon into charge. Understanding this highly-efficient process could have important implications for future solar cell devices, and the potential novelty of bio-inspired devices is highlighted by the recent discovery of delocalised PPC exciton states and unexpectedly long-lasting quantum coherence in their dynamics at room temperature.
In a recent J. Phy. Chem. Lett. article, Cole, Chin, Hine, Haynes and Payne report on progress towards a fully ab initio parametrisation of the Hamiltonian describing excitonic transport in the Fenna-Matthews-Olson bacterial light-harvesting complex. The dependence of local optical band gaps on long-ranged electrostatics requires the use of linear-scaling DFT, along with recent developments in the computation of excited states. Comparisons between simulated and experimental optical spectra point toward future work that may help to elucidate important design principles in these nanoscale devices.
Investigation of many-body effects in the kernel of hemoglobin for ligand binding
Metalloporphyrin systems, such as heme, play a central role in biochemistry. The ability of such molecules to reversibly bind small ligands is vital for life, particularly in heme, which can bind diatomic molecules such as O2 and CO. Crucially, heme is the primary transport molecule in human respiration, but whereas O2 binds reversibly, CO binds irreversibly!
Recent work soon to appear in Physical Review Letters, by Cedric Weber, David O'Regan and others, used LS-DFT+DMFT (Linear-Scaling Density Functional Theory + Dynamical Mean-Field Theory, using ONETEP) to study the binding of oxygen and carbon monoxide to the heme molecule. They found that the many-body ground-state is entangled, and that a 3d orbital-selection process occurs beyond a critical value of the Hund's exchange coupling parameter J, by which out-of-plane orbital hybridization is enhanced and the difference of ligand binding affinities is strongly reduced. This work offers a very detailed picture of the microscopic mechanisms of diatomic ligand binding to heme, and is among the first applications of DFT+DFMT to molecules, including total-energies, spectral properties in very good agreement with experiment, and transient magnetic response calculations.
- Importance of many body effects in the kernel of Haemoglobin for ligand binding, C. Weber, D. D. O'Regan, N. D. M. Hine, P. B. Littlewood, G. Kotliar and M. C. Payne, Physical Review Letters 110, 106402 (2013).
Investigation of protein-protein interactions with ONETEP
Biomolecular assemblies such as protein-protein complexes are crucial functional components of the cell and are essential for many processes such as for example the synthesis of proteins from messenger RNA by the ribosome, or the repair of breaks in the DNA by the complex between the BRCA2 and RAD51 proteins. With ONETEP researchers in Cambridge and Southampton have been able to study the entire complex between human RAD51 and BRCA2 elucidating the mechanism of interaction in terms of the location and strength of "energetic hotspots", which are amino-acids that contribute the bulk of the stabilisation during binding. Furthermore, by performing natural bond orbital (NBO) analysis on the density matrix from the ONETEP calculations they have found that hyperconjugative interactions between non-bonding electron pairs and antibonding pi* NBOs provide a hitherto unknown stabilization mechanism for the protein conformation that leads to maximum interaction between the energetic hotspots. The ability to study processes at protein-protein interfaces opens up new ways of probing chemical and physical processes that happen inside the cell.
Electron density polarisation at the interface between RAD51 and the BRC4 domain of BRCA2
- Natural Bond Orbital Analysis in Linear-Scaling Density Functional Theory Calculations: application to a protein-protein interface
L. P. Lee, D. J. Cole, M. C. Payne, and C.-K. Skylaris, Submitted.
- Interrogation of the Protein-Protein Interactions between Human BRCA2 BRC Repeats and RAD51 Reveals Atomistic Determinants of Affinity, D. J. Cole, E. Rajendra, M. Roberts-Thomson, B. Hardwick, G. J. McKenzie, M. C. Payne, A. R. Venkitaraman and C.-K. Skylaris, PLoS Comput Biol 7(7): e1002096 (2011).
- Protein-protein interactions from linear-scaling first-principles quantum-mechanical calculations, D. J. Cole, C.-K. Skylaris, E. Rajendra, A. R. Venkitaraman and M. C. Payne, Europhysics Letters 91(3), 37004 (2010).
Towards drug optimisation with ONETEP
The computational simulation of the strength with which drugs bind to proteins and other biomolecular entities can offer important cost-saving guidance at the early stages of the drug development process. Typically such simulations are performed with classical force fields. The empirical nature of force fields often means that interactions may not be represented with the required accuracy, especially for new drug candidates which may lie outside the function or parameter space that was used to generate the force field. Researchers in Southampton in collaboration with researhers in Boehringer Ingelheim and Accelrys have been using calculations with ONETEP on entire protein-drug complexes in order to obtain more accurate interactions and better estimates of free energies of receptor-drug binding. This work goes hand in hand with other recent and ongoing developments in ONETEP such as dispersion interactions, solvent effects, electrostatic embedding, ab initio molecular dynamics, and statistical mechanics techniques for obtaining free energies.
10151-atom calculation with ONETEP on the complex of the T4 Lysozyme L99A/M102Q protein and ligand in water and counterions.
- Large-scale DFT calculations in implicit solvent - a case study on the T4 lysozyme L99A/M102Q protein
J. Dziedzic, S. J. Fox, T. Fox, C. S. Tautermann, and C.-K. Skylaris, Submitted.
- Electrostatic embedding in large-scale first principles quantum mechanical calculations on biomolecules, S. J. Fox., C. Pittock, T. Fox, C. Tautermann, N. Malcolm, and C.-K. Skylaris.
- First principles-based calculations of free energy of binding: application to ligand binding in a self-assembling superstructure, S. Fox, H. Wallnoefer, T. Fox, C. Tautermann , and C.-K. Skylaris, J. Chem. Theor. Comput. 7, 1102 (2011).