16 research outputs found
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Lattice models for photosynthetic membrane stacks
Proteins in photosynthetic membranes can organize into patterned arrays that span the membrane's lateral size. Attractions between proteins in different layers of a membrane stack play a key role in this ordering, as has been demonstrated by both empirical and computational methods. The architecture of thylakoid membranes, depending on physiological conditions, also may create circumstances for inter-layer interactions that instead disfavor the high protein densities of ordered arrangements. This dissertation introduces several statistical mechanical models for exploring the interplay between these opposing forces and for characterizing phases that reflect the periodic geometry of stacked thylakoid membrane discs. First, we propose a lattice model that roughly accounts for proteins' attraction within a layer and across the stromal gap, steric repulsion across the lumenal gap, and regulation of protein density by exchange with the stroma lamellae. Mean field analysis and computer simulation reveal a broken-symmetry striped phase disrupted at both high and low extremes of density. We expect that the widely varying light and stress conditions in higher plants explore the space of protein density and interaction strength broadly. The phase transitions we identify should thus lie within or near the range of naturally occurring conditions. Second, we expand upon this lattice description, allowing the thickness of each thylakoid's lumenal gap to fluctuate. This fluctuating-gap model introduces the possibility of mechanical control of photosynthetic function. We monitor how changing gap thickness affects mean protein occupation on both sides of the discs. Via mean field analysis and computer simulation we find even richer phase behavior for this model, featuring transitions that originate in long-ranged protein interactions mediated by lumenal gap fluctuations. These results suggest that compression or expansion of lumenal gaps could lead to sudden and dramatic changes in the population and spatial patterning of photosynthetic proteins. Taken together, the lattice models we have constructed and explored provide a framework for minimalistic modeling of the physics underlying structure and function of photosynthetic membranes
VPT2+K Spectroscopic Constants and Matrix Elements of the Transformed Vibrational Hamiltonian of a Polyatomic Molecule with Resonances Using Van Vleck Perturbation Theory
Vibrational levels of polyatomic molecules are analysed with Van Vleck perturbation theory to connect experimental energy levels to computed molecular potential energy surfaces. Vibrational matrix elements are calculated from a quartic potential function via second-order Van Vleck perturbation theory, a procedure that treats both weak and strong interactions among vibrational states by approximately block-diagonalising the vibrational Hamiltonian. A clear and complete derivation of anharmonic and resonance constants as well as general expressions for both on- and off-diagonal matrix elements of the transformed Hamiltonian is presented. The equations are written in partial fraction form and as a constant multiplied by a harmonic oscillator matrix element to facilitate removing the effect of strongly interacting resonant states both in analytical formulae and in computer code. The derived equations are validated numerically, and results for the isotopomers of formaldehyde (H2CO, HDCO, D2CO) are included. The implications of the equations on zero-point energy calculations and experimental fits are discussed. The VPT2+K method is defined by these results for use in fitting and calculating vibrational energy levels
Theoretical characterization of the spectral density of the water-soluble chlorophyll-binding protein from combined quantum mechanics/molecular mechanics molecular dynamics simulations
Over the past decade, both experimentalists and theorists have worked to develop methods to describe pigment-protein coupling in photosynthetic light-harvesting complexes in order to understand the molecular basis of quantum coherence effects observed in photosynthesis. Here we present an improved strategy based on the combination of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations and excited-state calculations to predict the spectral density of electronic-vibrational coupling. We study the water-soluble chlorophyll-binding protein (WSCP) reconstituted with Chl a or Chl b pigments as the system of interest and compare our work with data obtained by Pieper and co-workers from differential fluorescence line-narrowing spectra (Pieper et al. J. Phys. Chem. B 2011, 115 (14), 4042−4052). Our results demonstrate that the use of QM/MM MD simulations where the nuclear positions are still propagated at the classical level leads to a striking improvement of the predicted spectral densities in the middle- and high-frequency regions, where they nearly reach quantitative accuracy. This demonstrates that the so-called 'geometry mismatch' problem related to the use of low-quality structures in QM calculations, not the quantum features of pigments high-frequency motions, causes the failure of previous studies relying on similar protocols. Thus, this work paves the way toward quantitative predictions of pigment-protein coupling and the comprehension of quantum coherence effects in photosynthesis
Remembering the work of Phillip L. Geissler: A coda to his scientific trajectory
Phillip L. Geissler made important contributions to the statistical mechanics
of biological polymers, heterogeneous materials, and chemical dynamics in
aqueous environments. He devised analytical and computational methods that
revealed the underlying organization of complex systems at the frontiers of
biology, chemistry, and materials science. In this retrospective, we celebrate
his work at these frontiers
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
VPT2+K Spectroscopic Constants and Matrix Elements of the Transformed Vibrational Hamiltonian of a Polyatomic Molecule with Resonances Using Van Vleck Perturbation Theory
Vibrational levels of polyatomic molecules are analyzed with Van Vleck perturbation theory to connect experimental energy levels to computed molecular potential energy surfaces. Vibrational matrix elements are calculated from a quartic potential function via second order Van Vleck perturbation theory, a procedure that treats both weak and strong interactions among vibrational states by approximately block-diagonalizing the vibrational Hamiltonian. A clear and complete derivation of anharmonic and resonance constants as well as general expressions for both on- and off-diagonal matrix elements of the transformed Hamiltonian is presented. The equations are written in partial fraction form and as a constant multiplied by a harmonic oscillator matrix element to facilitate removing the effect of strongly interacting resonant states both in analytical formulae and in computer code. The derived equations are validated numerically, and results for formaldehyde are included. The VPT2+K method is defined by these results for use in fitting and calculating vibrational energy levels
Transforming the Vibrational Hamiltonian of a Polyatomic Molecule Using Van Vleck Perturbation Theory
The goal of analyzing vibrational levels of polyatomic molecules with Van Vleck perturbation theory is to connect experimental and theoretical approaches for determining molecular potential energy surfaces. Chemists model reactivity of molecules along potential energy surfaces, which are functions of the internal coordinates of the molecule. Vibrations move along these coordinates, so measuring vibrations experimentally characterizes the potential energy surface. Vibrational energy levels are calculated from a quartic potential function via Van Vleck perturbation theory, a procedure that approximately diagonalizes the vibrational Hamiltonian. The matrix elements of the transformed Hamiltonian have been derived, and some of the equations are presented. A new computational technique, VPT2+K, will be defined by these results and used to calculate vibrational states