A site-dependent spectral density system-bath model of the Fenna-Matthews-Olsen (FMO) pigment-protein complex is developed using results from ground-state molecular mechanics simulations together with a partial charge difference model for how the long-range contributions to the chromophore excitation energies fluctuate with environmental configuration. A discussion of how best to consistently process the chromophore excitation energy fluctuation correlation functions calculated in these classical simulations to obtain reliable site-dependent spectral densities is presented. The calculations reveal that chromophores that are close to the protein-water interface can experience strongly dissipative environmental interactions characterized by reorganization energies that can be as much as 2-3 times those of chromophores that are buried deep in the hydrophobic protein scaffolding. Using a linearized density matrix quantum propagation method, we demonstrate that the inhomogeneous system-bath model obtained from our site-dependent spectral density calculations gives results consistent with experimental dissipation and dephasing rates. Moreover, we show that this model can simultaneously enhance the energy-transfer rate and extend the decoherence time. Finally, we explore the influence of initially exciting different chromophores and mutating local environments on energy transfer through the network. These studies suggest that different pathways, selected by varying initial photoexcitation, can exhibit significantly different relaxation times depending on whether the energy-transfer path involves chromophores at the protein-solvent interface or if all chromophores in the pathway are buried in the protein.

The light harvesting 2 (LH2) antenna complex from purple photosynthetic bacteria is an efficient natural excitation energy carrier with well-known symmetric structure, but the molecular level design principle governing its structure-function relationship is unknown. Our all-atomistic simulations of nonnatural analogues of LH2 as well as those of a natural LH2 suggest that nonnatural sizes of LH2-like complexes could be built. However, stable and consistent hydrogen bonding (HB) between bacteriochlorophyll and the protein is shown to be possible only near naturally occurring sizes, leading to significantly smaller disorder than for nonnatural ones. Extensive quantum calculations of intercomplex exciton transfer dynamics, sampled for a large set of disorder, reveal that taming the negative effect of disorder through a reliable HB as well as quantum delocalization of the exciton is a critical mechanism that makes LH2 highly functional, which also explains why the natural sizes of LH2 are indeed optimal.

Fibril formation from amyloidogenic peptides is a hallmark of a wide range of diseases, including Alzheimer's disease and type II diabetes. Characterization of the aggregation process should include intrinsic factors, such as sequence variation, and extrinsic factors, such as crowding effects. To this end, we examined the interactions of dimers composed of residues 20-29 of human islet amyloid polypeptide (hIAPP), which form fibrils in vitro, and the nonamyloidogenic rat IAPP (rIAPP) using molecular dynamics simulations modeled at different peptide concentrations. There is a substantial free energy barrier to unbind the hIAPP dimer whereas no barrier exists for separating the rIAPP dimer. The profound differences in the free energy landscapes of the rIAPP and hIAPP dimers explains the lack of fibril formation in hIAPP upon substitution of the C-terminal residues by proline. Enhancing the extent of crowding has a substantial effect on both the barrier for separating a hIAPP beta-sheet dimer and the formation of potential beta-sheet nucleation sites. Our results show that the propensity for forming nucleation sites is dependent not only on the amino-acid sequence but also on the context in which it is found.

Light harvesting 2 (LH2) complex is the primary component of the photosynthetic unit of purple bacteria that is responsible for harvesting and relaying excitons. The electronic absorption line shape of LH2 contains two major bands at 800 and 850 nm wavelength regions. Under low light conditions, some species of purple bacteria replace LH2 with light harvesting 3 (LH3), a variant form with almost the same structure as the former but with distinctively different spectral features. The major difference between the absorption line shapes of LH2 and LH3 is the shift of the 850 nm band of the former to a new 820 nm region. The microscopic origin of this difference has been the subject of some theoretical/computational investigations. However, the genuine molecular level source of such a difference is not clearly understood yet. This work reports a comprehensive computational study of LH2 and LH3 complexes so as to clarify different molecular level features of LH2 and LH3 complexes and to construct simple exciton-bath models with a common form. All-atomistic molecular dynamics simulations of both LH2 and LH3 complexes provide detailed molecular level structural differences of bacteriochlorophylls (BChls) in the two complexes, in particular, in their patterns of hydrogen bonding (HB) and torsional angles of the acetyl group. Time-dependent density functional theory calculation of the excitation energies of BChls for structures sampled from the MD simulations suggests that the observed differences in the HB and torsional angles cannot fully account for the experimentally observed spectral shift of LH3. Potential sources that can explain the actual spectral shift of LH3 are discussed, and their magnitudes are assessed through fitting of experimental line shapes. These results demonstrate the feasibility of developing simple exciton-bath models for both LH2 and LH3, which can be employed for large-scale exciton quantum dynamics in their aggregates.

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Characterization of the molecular interactions that stabilize the folded state of proteins including hydrogen bond formation, solvation, molecular crowding, and interaction with membrane environments is a fundamental goal of theoretical biophysics. Inspired by recent experimental studies by Gai and co-workers, we have used molecular dynamics simulations to explore the structure and dynamics of the alanine-rich AKA 2 peptide in bulk solution and in a reverse micelle environment. The simulated structure of the reverse micelle shows substantial deviations from a spherical geometry. The AKA 2 peptide is observed to (1) remain in a helical conformation within a spherically constrained reverse micelle and (2) partially unfold when simulated in an unconstrained reverse micelle environment, in agreement with experiment. While aqueous solvation is found to stabilize the N-and C-termini random coil portions of the peptide, the helical core region is stabilized by significant interaction between the nonpolar surface of the helix and the aliphatic chains of the AOT surfactant. The results suggest an important role for nonpolar peptide-surfactant and peptide-lipid interactions in stabilizing helical geometries of peptides in reverse micelle environments.

Knowledge of how intermolecular interactions of amyloid-forming proteins cause protein aggregation and how those interactions are affected by sequence and solution conditions is essential to our understanding of the onset of many degenerative diseases. Of particular interest is the aggregation of the amyloid-β (Aβ) peptide, linked to Alzheimer's disease, and the aggregation of the Sup35 yeast prion peptide, which resembles the mammalian prion protein linked to spongiform encephalopathies. To facilitate the study of these important peptides, experimentalists have identified small peptide congeners of the full-length proteins that exhibit amyloidogenic behavior, including the KLVFFAE sub-sequence, Aβ 16−22 , and the GNNQQNY subsequence, Sup35 7−13 . In this study, molecular dynamics simulations were used to examine these peptide fragments encapsulated in reverse micelles (RMs) in order to identify the fundamental principles that govern how sequence and solution environment influence peptide aggregation. Aβ 16−22 and Sup35 7−13 are observed to organize into anti-parallel and parallel β-sheet arrangements. Confinement in the sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse micelles is shown to stabilize extended peptide conformations and enhance peptide aggregation. Substantial fluctuations in the reverse micelle shape are observed, in agreement with earlier studies. Shape fluctuations are found to facilitate peptide solvation through interactions between the peptide and AOT surfactant, including direct interaction between non-polar peptide residues and the aliphatic surfactant tails. Computed amide I IR spectra are compared with experimental spectra and found to reflect changes in the peptide structures induced by confinement in the RM environment. Furthermore, examination of the rotational anisotropy decay of water in the RM demonstrates that the water dynamics are sensitive to the presence of peptide as well as the peptide sequence. Overall, our results demonstrate that the RM is a complex confining environment where substantial direct interaction between the surfactant and peptides plays an important role in determining the resulting ensemble of peptide conformations. By extension the results suggest that similarly complex sequence-dependent interactions may determine conformational ensembles of amyloid-forming peptides in a cellular environment. © 2014 AIP Publishing LLC.

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