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.

Rationale & Objective: Biomarkers that provide reliable evidence of future diabetic kidney disease (DKD) are needed to improve disease management. In a cross-sectional study, we previously identified thirteen urine metabolites that were reduced in DKD compared with healthy controls. Here, we evaluated associations of these thirteen metabolites with future DKD progression.

R-loops are three-stranded nucleic acid structures formed from the hybridization of RNA and DNA during transcription. While the pathological consequences of R-loops have been well-studied to date, the locations, classes, and dynamics of physiological R-loops remain poorly understood. R-loop mapping studies provide insight into R-loop dynamics, but their findings are challenging to generalize. This is due to the narrow biological scope of individual studies, the limitations of each mapping modality, and, in some cases, poor data quality. In this study, we reprocessed 693 R-loop mapping datasets from a wide array of biological conditions and mapping modalities. From this data resource, we developed an accurate method for R-loop data quality control, and we reveal the extent of poor-quality data within previously published studies. We then identified a set of high-confidence R-loop mapping samples and used them to define consensus R-loop sites called “R-loop regions” (RL regions). In the process, we revealed the stark divergence between S9.6 and dRNH-based R-loop mapping methods and identified biologically meaningful subtypes of both constitutive and variable R-loops. Taken together, this work provides a much-needed method to assess R-loop data quality and reveals intriguing aspects of R-loop biology.

We show that quantum time correlation functions including electronically nonadiabatic effects can be computed by using an approach in which their path integral expression is linearized in the difference between forward and backward nuclear paths while the electronic component of the amplitude, represented in the mapping formulation, can be computed exactly, leading to classical-like equations of motion for all degrees of freedom. The efficiency of this approach is demonstrated in some simple model applications. In statistical mechanics, time correlation functions are central quantities bridging the microscopic dynamics and fluctuations of a given system with macroscopic, phenomenological quantities, such as transport coefficient, relaxation times, and rates (1, 2). Although relatively standard numerical methods provide a viable tool for their evaluation in classical systems (3, 4), full quantum mechanical calculation of time correlations functions is currently out of the realm of affordable computation. Consequently, many approximate techniques have been developed to tackle this problem (5-9). In this article, we present a mixed quantum-classical approach, belonging to the family of so-called linearization methods (10)(11)(12)(13)(14)(15), that addresses the evaluation of time correlation functions of nuclear or electronic operators evolving in the presence of nonadiabatic effects. TheoryWe begin by rewriting the function in a basis set defined as the tensor product of nuclear positions and diabatic electronic statesHere, the Hamiltonian Ĥ contains the nuclear kinetic energy and an electronic part, ĥ el , with matrix elements h ,Ј (R), is the density matrix of the system, and we have chosen the operator B to be diagonal in the nuclear space. A convenient representation to account for the effects of the electronic transitions on the nuclear degrees of freedom is offered by the mapping Hamiltonian method (16-23). In this context, the n diabatic states are substituted by n harmonic oscillators with occupation number limited to 0 or 1, i.e., ͉␣͘ 3 ͉m ␣ ͘ ϭ ͉0 1 , . . . , 1 ␣ , . . . , 0 n ͘, and the electronic Hamiltonian becomeswhere q and p are the positions and momenta of the oscillators. While leaving the nuclear motion unaltered, the mapping simplifies the electronic problem considerably and has been applied to study nonadiabatic dynamics in many semiclassical calculations (16-23). Its advantages become apparent once a hybrid momentum-coordinate representation is introduced for the propagators in the correlation function, for examplewhereͬ.[4]The transition amplitude between mapping states m ␣ and m ␤ is determined by a quadratic Hamiltonian that depends parametrically on the nuclear path. Thus, this amplitude can be evaluated exactly, for example, by using a semiclassical expression. A particularly convenient semiclassical choice, both computationally and from a theoretical viewpoint, is the Herman-Kluk representation (24), which provides us with the following expression for the amplitude ͗m ␤ ͉e Ϫ͑i/ -h͒ĥm͑RN...