Atoms-in-molecules study of the genetically encoded amino acids. III. Bond and atomic properties and their correlations with experiment including mutation-induced changes in protein stability and genetic coding

This article presents a study of the molecular charge distributions of the genetically encoded amino acids (AA), one that builds on the previous determination of their equilibrium geometries and the demonstrated transferability of their common geometrical parameters. The properties of the charge distributions are characterized and given quantitative expression in terms of the bond and atomic properties determined within the quantum theory of atoms-in-molecules (QTAIM) that defines atoms and bonds in terms of the observable charge density. The properties so defined are demonstrated to be remarkably transferable, a reflection of the underlying transferability of the charge distributions of the main chain and other groups common to the AA. The use of the atomic properties in obtaining an understanding of the biological functions of the AA, whether free or bound in a polypeptide, is demonstrated by the excellent statistical correlations they yield with experimental physicochemical properties. A property of the AA side chains of particular importance is the charge separation index (CSI), a quantity previously defined as the sum of the magnitudes of the atomic charges and which measures the degree of separation of positive and negative charges in the side chain of interest. The CSI values provide a correlation with the measured free energies of transfer of capped side chain analogues, from the vapor phase to aqueous solution, yielding a linear regression equation with r2 = 0.94. The atomic volume is defined by the van der Waals isodensity surface and it, together with the CSI, which accounts for the electrostriction of the solvent, yield a linear regression (r2 = 0.98) with the measured partial molar volumes of the AAs. The changes in free energies of transfer from octanol to water upon interchanging 153 pairs of AAs and from cyclohexane to water upon interchanging 190 pairs of AAs, were modeled using only three calculated parameters (representing electrostatic and volume contributions) yielding linear regressions with r2 values of 0.78 and 0.89, respectively. These results are a prelude to the single-site mutation-induced changes in the stabilities of two typical proteins: ubiquitin and staphylococcal nuclease. Strong quadratic correlations (r2 approximately 0.9) were obtained between DeltaCSI upon mutation and each of the two terms DeltaDeltaH and TDeltaDeltaS taken from recent and accurate differential scanning calorimetry experiments on ubiquitin. When the two terms are summed to yield DeltaDeltaG, the quadratic terms nearly cancel, and the result is a simple linear fit between DeltaDeltaG and DeltaCSI with r2 = 0.88. As another example, the change in the stability of staphylococcal nuclease upon mutation has been fitted linearly (r2 = 0.83) to the sum of a DeltaCSI term and a term representing the change in the van der Waals volume of the side chains upon mutation. The suggested correlation of the polarity of the side chain with the second letter of the AA triplet genetic codon is given concrete expression in a classification of the side chains in terms of their CSI values and their group dipole moments. For example, all amino acids with a pyrimidine base as their second letter in mRNA possess side-chain CSI < or = 2.8 (with the exception of Cys), whereas all those with CSI > 2.8 possess an purine base. The article concludes with two proposals for measuring and predicting molecular complementarity: van der Waals complementarity expressed in terms of the van der Waals isodensity surface and Lewis complementarity expressed in terms of the local charge concentrations and depletions defined by the topology of the Laplacian of the electron density. A display of the experimentally accessible Laplacian distribution for a folded protein would offer a clear picture of the operation of the "stereochemical code" proposed as the determinant in the folding process.     

Probing the effect of nitro groups in nitramine based energetic molecules: a DFT and charge density study

The structure, electron density distribution, energetic and electrostatic properties of simple nitramine based energetic TMA, DMNA, MDA and TNA molecules were determined using density functional theory (B3LYP) with the 6-311G^** and aug-cc-pVDZ basis sets coupled with Bader's theory of atoms in molecules. In the NO₂ group substituted molecules, the N–N bond distance increases with the increase of NO₂ groups, whereas in C–N bonds, this effect is relatively less, and the distances are almost equal. The topological analysis of electron density reveals that the electron density ρ_bcp(r) of C–N and N–N bonds are significantly decreasing with the increase of NO₂ groups in the nitramine molecules. The Laplacian of electron density ▽²ρ_bcp(r) of N–NO₂ bonds [DMNA: ? 16.7 eÅ^? 5, MDA: ? 12.8 eÅ^? 5 and TNA: ? 7.9 eÅ^? 5] of the molecules are relatively less negative, and the values also decrease with the increase of NO₂ groups; this implies that the charge concentration decreases with the increase of NO₂ groups, which leads to weakening the N–N bonds of the molecules. The isosurface of molecular electrostatic potential displays high electronegative regions around the NO₂ groups. The oxygen balance OB₁₀₀ of the molecules increases as the number of NO₂ group increases in the molecules, in which, the TNA molecule having maximum OB₁₀₀ value [+7.89]. The band gap, heat of detonation, bond dissociation energy and charge imbalance are predominantly depends on the number of NO₂ group present in the molecule. The charge imbalance parameter (ν) has been calculated for all molecules, which reveals that TNA is a highly sensitive molecule, the corresponding ν value is 0.047.     

Closing the Loop on Cadmium - An Assessment of the Material Cycle of Cadmium in the U.S. (11 pp)

Goal, Scope and Background In this study, the major flows of cadmium in the U.S. economy are quantified and the primary sinks are identified to gauge the need for additional policy to minimize the potential human health and ecosystem risks associated with these flows. Because of the concurrent occurrence of cadmium and zinc in ore, we also consider the relevant portions of the material cycle of zinc. Methods We estimated the flows of cadmium through U.S. manufacturing using a mass balance approach with data provided by the U.S. Geological Survey's Minerals Yearbook. Cadmium emissions factors were created using facility specific information found in the U.S. Toxics Release Inventory and were used to model future losses. Data gaps were filled through review of relevant literature. We modeled the import and sales of nickel-cadmium batteries with rechargeable battery usage trends and estimates of market share by battery chemistry. Results and Conclusion Primary cadmium in the U.S. is almost exclusively produced as a co-product of zinc. Almost all zinc and cadmium mined in the U.S. is exported to foreign smelters as ore concentrate. We estimate that the bulk of cadmium consumed in the U.S. economy (~90%) is imported in the form of nickel-cadmium rechargeable batteries. These batteries can be divided into the larger wet-cells and portable rechargeable batteries (PRB). The collection rate for the recycling of large wet cells was found to be high (80%) while the collection rate for PRBs is low (5-20%). The Rechargeable Battery Recycling Corporation (RBRC) is responsible for the collection of these batteries which are recycled exclusively by the International Materials Reclamation Company (INMETCO). The remaining PRBs are generally disposed of in municipal solid waste (MSW) landfills. This study provides a detailed substance flow analysis of U.S. stocks and flows of cadmium in products, however additional research is needed to better quantify the associated exposures and risks. Recommendation and Perspective Based on our analysis, we make four recommendations. First we suggest that if cadmium is to be used, it should be used in long-lived products that can be easily collected and recycled with minimal losses. Second, continued cadmium use should be coupled with renewed efforts on the part of policy-makers to encourage the collection and recycling of cadmium-bearing products. At present, consumers do not see the environmental cost associated with the proper disposal of the cadmium content of NiCd batteries. Policy options for improving recycling rates include collecting deposits and providing rewards for the return of spent batteries, taxing or otherwise discouraging discarding PRBs in municipal solid waste, and providing incentives for extended producer responsibility. Third, we highlight the importance of the connection between zinc mining and the supply of cadmium in designing an effective policy to manage the risks associated with cadmium. Fourth, we recommend that policy measures be taken to provide the necessary data required to improve our understanding of the flow of cadmium into the U.S. in the form of product imports and the amount of cadmium lost or disposed of by recycling processes.     

Mutations in algal and cyanobacterial Photosystem I that independently affect the yield of initial charge separation in the two electron transfer cofactor branches

In Photosystem I, light-induced electron transfer can occur in either of two symmetry-related branches of cofactors, each of which is composed of a pair of chlorophylls (ec2_A/ec3_A or ec2_B/ec3_B) and a phylloquinone (PhQ_A or PhQ_B). The axial ligand to the central Mg^2 + of the ec2_A and ec2_B chlorophylls is a water molecule that is also H-bonded to a nearby Asn residue. Here, we investigate the importance of this interaction for charge separation by converting each of the Asn residues to a Leu in the green alga, Chlamydomonas reinhardtii, and the cyanobacterium, Synechocystis sp. PCC6803, and studying the energy and electron transfer using time-resolved optical and EPR spectroscopy. Nanosecond transient absorbance measurements of the PhQ to F_X electron transfer show that in both species, the PsaA-N604L mutation (near ec2_B) results in a ~ 50% reduction in the amount of electron transfer in the B-branch, while the PsaB-N591L mutation (near ec2_A) results in a ~ 70% reduction in the amount of electron transfer in the A-branch. A diminished quantum yield of P₇₀₀⁺ PhQ^? is also observed in ultrafast optical experiments, but the lower yield does not appear to be a consequence of charge recombination in the nanosecond or microsecond timescales. The most significant finding is that the yield of electron transfer in the unaffected branch did not increase to compensate for the lower yield in the affected branch. Hence, each branch of the reaction center appears to operate independently of the other in carrying out light-induced charge separation.     

Molecular dynamics study of the primary charge separation reactions in Photosystem I: Effect of the replacement of the axial ligands to the electron acceptor A0

Molecular dynamics (MD) calculations, a semi-continuum (SC) approach, and quantum chemistry (QC) calculations were employed together to investigate the molecular mechanics of ultrafast charge separation reactions in Photosystem I (PS I) of Thermosynechococcus elongatus. A molecular model of PS I was developed with the aim to relate the atomic structure with electron transfer events in the two branches of cofactors. A structural flexibility map of PS I was constructed based on MD simulations, which demonstrated its rigid hydrophobic core and more flexible peripheral regions. The MD model permitted the study of atomic movements (dielectric polarization) in response to primary and secondary charge separations, while QC calculations were used to estimate the direct chemical effect of the A_0A/A_0B ligands (Met or Asn in the 688/668 position) on the redox potential of chlorophylls A_0A/A_0B and phylloquinones A_1A/A_1B. A combination of MD and SC approaches was used to estimate reorganization energies λ of the primary (λ₁) and secondary (λ₂) charge separation reactions, which were found to be independent of the active branch of electron transfer; in PS I from the wild type, λ₁ was estimated to be 390 ± 20 mV, while λ₂ was estimated to be higher at 445 ± 15 mV. MD and QC approaches were used to describe the effect of substituting Met688_PsaA/Met668_PsaB by Asn688_PsaA/Asn668_PsaB on the energetics of electron transfer. Unlike Met, which has limited degrees of freedom in the site, Asn was found to switch between two relatively stable conformations depending on cofactor charge. The introduction of Asn and its conformation flexibility significantly affected the reorganization energy of charge separation and the redox potentials of chlorophylls A_0A/A_0B and phylloquinones A_1A/A_1B, which may explain the experimentally observed slowdown of secondary electron transfer in the M688N_PsaA variant. This article is part of a Special Issue entitled: Photosynthesis research for sustainability: Keys to produce clean energy.