Ionization Energies and Redox Potentials of Hydrated Transition Metal Ions: Evaluation of Domain-Based Local Pair Natural Orbital Coupled Cluster Approaches

Hydrated transition metal ions are prototypical systems that can be used to model properties of transition metals in complex chemical environments. These seemingly simple systems present challenges for computational chemistry and are thus crucial in evaluations of quantum chemical methods for spin-state and redox energetics. In this work, we explore the applicability of the domain-based pair natural orbital implementation of coupled cluster (DLPNO-CC) theory to the calculation of ionization energies and redox potentials for hydrated ions of all first transition row (3d) metals in the 2+/3+ oxidation states, in connection with various solvation approaches. In terms of model definition, we investigate the construction of a minimally explicitly hydrated quantum cluster with a first and second hydration layer. We report on the convergence with respect to the coupled cluster expansion and the PNO space, as well as on the role of perturbative triple excitations. A recent implementation of the conductor-like polarizable continuum model (CPCM) for the DLPNO-CC approach is employed to determine self-consistent redox potentials at the coupled cluster level. Our results establish conditions for the convergence of DLPNO-CCSD(T) energetics and stress the absolute necessity to explicitly consider the second solvation sphere even when CPCM is used. The achievable accuracy for redox potentials of a practical DLPNO-based approach is, on average, 0.13 V. Furthermore, multilayer approaches that combine a higher-level DLPNO-CCSD(T) description of the first solvation sphere with a lower-level description of the second solvation layer are investigated. The present work establishes optimal and transferable methodological choices for employing DLPNO-based coupled cluster theory, the associated CPCM implementation, and cost-efficient multilayer derivatives of the approach for open-shell transition metal systems in complex environments

Complete genome constellation of a caprine group A rotavirus strain reveals common evolution with ruminant and human rotavirus strains

This study reports the first complete genome sequence of a caprine group A rotavirus (GAR) strain, GO34. The VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5 genes of strain GO34, detected in Bangladesh, were assigned to the G6-P[1]-I2-R2-C2-M2-A11-N2-T6-E2-H3 genotypes, respectively. Strain GO34 was closely related to the VP4, VP6–7 and NSP4–5 genes of bovine GARs and the NSP1 gene of GO34 to an ovine GAR. Strain GO34 shared low nucleotide sequence identities (<90 %) with VP2–3 genes of other GARs, and was equally related to NSP3 genes of human, ruminant and camelid strains. The VP1, VP6 and NSP2 genes of strain GO34 also exhibited a close genetic relatedness to human G2, G6, G8 and G12 DS-1-like GARs, whereas the NSP1 of GO34 was also closely related to human G6P[14] strains. All these findings point to a common evolutionary origin of GO34 and bovine, ovine, antelope, guanaco and human G6P[14] GARs, although phylogenetically GO34 is not particularly closely related to any other rotavirus strains known to date

Inherited chromosomally integrated human herpesvirus 6 genomes are ancient, intact and potentially able to reactivate from telomeres

The genomes of human herpesviruses 6A and 6B (HHV-6A and HHV-6B) have the capacity to integrate into telomeres, the essential capping structures of chromosomes that play roles in cancer and ageing. About 1% of people worldwide are carriers of chromosomally integrated HHV-6 (ciHHV-6), which is inherited as a genetic trait. Understanding the consequences of integration for the evolution of the viral genome, for the telomere and for the risk of disease associated with carrier status is hampered by a lack of knowledge about ciHHV-6 genomes. Here, we report an analysis of 28 ciHHV-6 genomes and show that they are significantly divergent from the few modern non-integrated HHV-6 strains for which complete sequences are currently available. In addition ciHHV-6B genomes in Europeans are more closely related to each other than to ciHHV-6B genomes from China and Pakistan, suggesting regional variation of the trait. Remarkably, at least one group of European ciHHV-6B carriers has inherited the same ciHHV-6B genome, integrated in the same telomere allele, from a common ancestor estimated to have existed 24,500 ±10,600 years ago. Despite the antiquity of some, and possibly most, germline HHV-6 integrations, the majority of ciHHV-6B (95%) and ciHHV-6A (72%) genomes contain a full set of intact viral genes and therefore appear to have the capacity for viral gene expression and full reactivation. IMPORTANCE: Inheritance of HHV-6A or HHV-6B integrated into a telomere occurs at a low frequency in most populations studied to date but its characteristics are poorly understood. However, stratification of ciHHV-6 carriers in modern populations due to common ancestry is an important consideration for genome-wide association studies that aim to identify disease risks for these people. Here we present full sequence analysis of 28 ciHHV-6 genomes and show that ciHHV-6B in many carriers with European ancestry most likely originated from ancient integration events in a small number of ancestors. We propose that ancient ancestral origins for ciHHV-6A and ciHHV-6B are also likely in other populations. Moreover, despite their antiquity, all of the ciHHV-6 genomes appear to retain the capacity to express viral genes, and most are predicted to be capable of full viral reactivation. These discoveries represent potentially important considerations in immune-compromised patients, in particular in organ transplantation and in stem cell therapy

Ionization Energies and Aqueous Redox Potentials of Organic Molecules: Comparison of DFT, Correlated ab Initio Theory and Pair Natural Orbital Approaches

The calculation of redox potentials involves large energetic terms arising from gas phase ionization energies, thermodynamic contributions, and solvation energies of the reduced and oxidized species. In this work we study the performance of a wide range of wave function and density functional theory methods for the prediction of ionization energies and aqueous one-electron oxidation potentials of a set of 19 organic molecules. Emphasis is placed on evaluating methods that employ the computationally efficient local pair natural orbital (LPNO) approach, as well as several implementations of coupled cluster theory and explicitly correlated F12 methods. The electronic energies are combined with implicit solvation models for the solvation energies. With the exception of MP2 and its variants, which suffer from enormous errors arising at least partially from the poor Hartree–Fock reference, ionization energies can be systematically predicted with average errors below 0.1 eV for most of the correlated wave function based methods studies here, provided basis set extrapolation is performed. LPNO methods are the most efficient way to achieve this type of accuracy. DFT methods show in general larger errors and suffer from inconsistent behavior. The only exception is the M06-2X functional which is found to be competitive with the best LPNO-based approaches for ionization energies. Importantly, the limiting factor for the calculation of accurate redox potentials is the solvation energy. The errors in the predicted solvation energies by all continuum solvation models tested in this work dominate the final computed reduction potential, resulting in average errors typically in excess of 0.3 V and hence obscuring the gains that arise from choosing a more accurate electronic structure method

The U95 Protein of Human Herpesvirus 6B Interacts with Human GRIM-19: Silencing of U95 Expression Reduces Viral Load and Abrogates Loss of Mitochondrial Membrane Potential▿

To better understand the pathogenesis of human herpesvirus 6 (HHV-6), it is important to elucidate the functional aspects of immediate-early (IE) genes at the initial phase of the infection. To study the functional role of the HHV-6B IE gene encoding U95, we generated a U95-Myc fusion protein and screened a pretransformed bone marrow cDNA library for U95-interacting proteins, using yeast-two hybrid analysis. The most frequently appearing U95-interacting protein identified was GRIM-19, which belongs to the family of genes associated with retinoid-interferon mortality and serves as an essential component of the oxidative phosphorylation system. This interaction was verified by both coimmunoprecipitation and confocal microscopic coimmunolocalization. Short-term HHV-6B infection of MT-4 T-lymphocytic cells induced syncytial formation, resulted in decreased mitochondrial membrane potential, and led to progressively pronounced ultrastructural changes, such as mitochondrial swelling, myelin-like figures, and a loss of cristae. Compared to controls, RNA interference against U95 effectively reduced the U95 mRNA copy number and abrogated the loss of mitochondrial membrane potential. Our results indicate that the high affinity between U95 early viral protein and GRIM-19 may be closely linked to the detrimental effect of HHV-6B infection on mitochondria. These findings may explain the alternative cell death mechanism of expiration, as opposed to apoptosis, observed in certain productively HHV-6B-infected cells. The interaction between U95 and GRIM-19 is thus functionally and metabolically significant in HHV-6B-infected cells and may be a means through which HHV-6B modulates cell death signals by interferon and retinoic acid