Open-ended response theory with polarizable embedding:Multiphoton absorption in biomolecular systems

We present the theory and implementation of an open-ended framework for electric response properties at the level of Hartree–Fock and Kohn–Sham density functional theory that includes effects from the molecular environment modeled by the polarizable embedding (PE) model. With this new state-of-the-art multiscale functionality, electric response properties to any order can be calculated for molecules embedded in polarizable atomistic molecular environments ranging from solvents to complex heterogeneous macromolecules such as proteins. In addition, environmental effects on multiphoton absorption (MPA) properties can be studied by evaluating single residues of the response functions. The PE approach includes mutual polarization effects between the quantum and classical parts of the system through induced dipoles that are determined self-consistently with respect to the electronic density. The applicability of our approach is demonstrated by calculating MPA strengths up to four-photon absorption for the green fluorescent protein. We show how the size of the quantum region, as well as the treatment of the border between the quantum and classical regions, is crucial in order to obtain reliable MPA predictions

A combined quantum mechanics/molecular mechanics study of the one- and two-photon absorption in the green fluorescent protein

Submitted manuscript version. Publisher's version available at http://doi.org/10.1039/C2CP23537D.We present for the first time a QM/MM study of the one- and two-photon absorption spectra of the GFP chromophore embedded in the full protein environment described by an advanced quantum mechanically derived polarizable force field. The calculations are performed on a crystal structure of the green fluorescent protein (GFP) using the polarizable embedding density functional theory (PE-DFT) scheme. The importance of treating the protein environment explicitly with a polarizable force field and higher-order multipoles is demonstrated, as well as the importance of including water molecules close to the chromophore in the protein barrel. For the most advanced description we achieve good agreement with experimental findings, with a peak at 405 nm for the neutral and a peak at 475 nm for the anionic form of the GFP chromophore. The presence of a dark OPA state, as suggested by other studies to explain the discrepancies between OPA and TPA spectra, is not supported by our calculations

The Distinct Cases of Kosovo and South Ossetia: Deciding the Question of Independence on the Merits and International Law

The cases of Kosovo and South Ossetia provide two opportunities for the community of nations to reconcile the rights of Serbia and Georgia with the rights of the peoples within their borders. Instead of doing so, other countries used these cases for ideological and political posturing and continued to do so as of the end of 2008. This Note will review Kosovo and South Ossetia and attempt to take the politics out of an inherently political decision-whether or not to recognize them as independent states. Part I of this Note will review how the United Nations has approached the issues of autonomy, borders, secession, and minorities. It will also provide background on the doctrines of self-determination and the rights of states. Part II will set out the facts-as they are generally accepted-of Kosovo and South Ossetia and consider the differing opinions regarding independence of the two areas. Part III will review those opinions in light of the goals and doctrines of the United Nations and how it has approached these issues in the past. The Note concludes that recognition of independence of the states should be driven by legal arguments rather than political or social alliances and that the goals of the United Nations are best served by being steadfast in promoting multi-ethnicity within political entities; Kosovo and South Ossetia should be recognized as autonomous regions within Serbia and Georgia, respectively. The Note also concludes that domestic as well as international legal structures must be in place to make autonomy workable

Averaged Solvent Embedding Potential Parameters for Multiscale Modeling of Molecular Properties

Published version available in J. Chem. Theory Comput., 2016, 12 (4), pp 1684–1695. We derive and validate averaged solvent parameters for embedding potentials to be used in polarizable embedding quantum mechanics/molecular mechanics (QM/MM) molecular property calculations of solutes in organic solvents. The parameters are solvent-specific atom-centered partial charges and isotropic polarizabilities averaged over a large number of geometries of solvent molecules. The use of averaged parameters reduces the computational cost to obtain the embedding potential, which can otherwise be a rate-limiting step in calculations involving large environments. The parameters are evaluated by analyzing the quality of the resulting molecular electrostatic potentials with respect to full QM potentials. We show that a combination of geometry-specific parameters for solvent molecules close to the QM region and averaged parameters for solvent molecules further away allows for efficient polarizable embedding multiscale modeling without compromising the accuracy. The results are promising for the de- velopment of general embedding parameters for biomolecules, where the reduction in computational cost can be considerable

Understanding and predicting one- and two-photon absorption properties of molecular complexes

The papers of this thesis are not available in Munin: 1. A. H. Steindal, K. Ruud, L. Frediani, K. Aidas and J. Kongsted: 'Excitation energies in solution: the fully polarizable QM/MM/PCM method', Journal of Physical Chemistry B (2011), vol.115(12):3027–3037. Available at http://dx.doi.org/10.1021/jp1101913 2. A. H. Steindal, J. M. H. Olsen, L. Frediani, J. Kongsted and K. Ruud: 'Parallelization of the polarizable embedding scheme for higher-order response functions', Molecular Physics (2012), Vol. 110, no.19-20. Available at http://dx.doi.org/10.1080/00268976.2012.721016 3. A. H. Steindal, J. M. H. Olsen, K. Ruud, L. Frediani and J. Kongsted: 'A combined quantum mechanics and molecular mechanics study of the one- and two-photon absorption in the green fluorescent protein', Physical Chemistry Chemical Physics (2012), vol.14:5440-5451. Available at http://dx.doi.org/10.1039/C2CP23537D 4. M. T. P. Beerepoot, A. H. Steindal, J. M. H. Olsen, K. Ruud, L. Frediani, B. O. Brandsdal and J. Kongsted: 'A polarizable embedding DFT study of one-photon absorption in fluorescent proteins' (manuscript) 5. N. H. List, J. M. H. Olsen, H. J. Aa. Jensen, A. H. Steindal and J. Kongsted: 'Molecular-level insight into the spectral tuning mechanism of the DsRed chromophore', Journal of Physical Chemistry Letters (2012), vol.3(23):3513–3521. Available at http://dx.doi.org/10.1021/jz3014858This thesis presents the development of theoretical models for the calculations of one- and two-photon absorption, and computational studies on solvated systems and biomolecules. The photon-absorbing chromophore is described by density functional theory, while the effects of the surroundings are taken into account by means of polarizable embedding models. The theory and implementation of a three-layered fully polarizable method is presented in this thesis. In this method, the short-range electrostatic potential due to the solvent is treated by a polarizable molecular mechanics force field, while the long-range effects are described by a dielectric continuum. This QM/MM/PCM implementation was tested on three organic molecules solvated in water and shown to converge faster with respect to system size compared to calculations using quantum mechanics/molecular mechanics (QM/MM) only. Further, the parallelization of the QM/MM module in the Dalton program is decribed, making it possible to do calculations on large molecular systems with the use of modern supercomputers. This implementation was used to calculate the one- and two-photon absorption properties in fluorescent proteins, demonstrating the importance of describing the protein surrounding the chromophore by a polarizable embedding

Understanding and predicting one- and two-photon absorption properties of molecular complexes

This thesis presents the development of theoretical models for the calculations of one- and two-photon absorption, and computational studies on solvated systems and biomolecules. The photon-absorbing chromophore is described by density functional theory, while the effects of the surroundings are taken into account by means of polarizable embedding models. The theory and implementation of a three-layered fully polarizable method is presented in this thesis. In this method, the short-range electrostatic potential due to the solvent is treated by a polarizable molecular mechanics force field, while the long-range effects are described by a dielectric continuum. This QM/MM/PCM implementation was tested on three organic molecules solvated in water and shown to converge faster with respect to system size compared to calculations using quantum mechanics/molecular mechanics (QM/MM) only. Further, the parallelization of the QM/MM module in the Dalton program is decribed, making it possible to do calculations on large molecular systems with the use of modern supercomputers. This implementation was used to calculate the one- and two-photon absorption properties in fluorescent proteins, demonstrating the importance of describing the protein surrounding the chromophore by a polarizable embedding

Electronic circular dichroism of fluorescent proteins: A computational study

The electronic circular dichroism (ECD) properties of the green fluorescent protein and other fluorescent proteins have been calculated with density functional theory. The influence of different embedding models on the ECD signal of the chromophore has been investigated by modeling the protein environment by the polarizable continuum model (QM/PCM), by the polarizable embedding model (PE-QM/MM), by treating the minimal environment quantum mechanically at the same footing as the chromophore (QM/QM), and by adding the remaining part of the protein by means of PCM (QM/QM/PCM). The rotatory strength is found to be more sensitive than the oscillatory strength to changes in the geometry of the chromophore and its surroundings and to the type of embedding model used. In general, explicit embedding of the surrounding protein (PE-QM/MM or QM/QM) induces an increase in the rotatory strength of the chromophore. Explicit inclusion of the whole protein through polarizable embedding is found to be an affordable embedding model that gives the correct sign of the rotatory strength for all fluorescent proteins. PCM is useful as a first approximation to protein environment effects, but as a rule seems to underestimate the rotatory strength

Convergence of environment polarization effects in multiscale modeling of excitation energies

We present a systematic investigation of the influence of polarization effects from a surrounding medium on the excitation energies of a chromophore. We use a combined molecular dynamics and polarizable embedding time-dependent density functional theory (PE-TD-DFT) approach for chromophores in pro- teins and in homogeneous solvents. The mutual polarization between the chromophore and its surround- ings is included in the PE-TD-DFT approach through the use of induced dipoles, placed on all atoms in the classical region, and self-consistent optimization of the quantum and classical polarizable regions. By varying the subset of sites in the environment for which atomic polarizabilities are included, we inves- tigate to what distance from the quantum region explicit polarization effects need to be taken into account in order to provide converged excitation energies. Our study gives new insight into the range of polarization interactions for chromophores in different chemical environments. We find that the rate of convergence of excitation energies with respect to polarization cut-off is much slower for chromoph- ores in an ordered environment such as a protein than for chromophores in a homogeneous medium such as a solvent. We show that this in part is related to the (partial) charges in the protein. Our results provide insight into how to define a representation of complex environments of different kinds in an accurate and affordable way