Sequential decoupling of negative-energy states in Douglas-Kroll-Hess theory

Here, we review the historical development, current status, and prospects of Douglas--Kroll--Hess theory as a quantum chemical relativistic electrons-only theory.Comment: 15 page

Prediction of inter-particle adhesion force from surface energy and surface roughness

Fine powder flow is a topic of great interest to industry, in particular for the pharmaceutical industry; a major concern being their poor flow behavior due to high cohesion. In this study, cohesion reduction, produced via surface modification, at the particle scale as well as bulk scale is addressed. The adhesion force model of Derjaguin-Muller-Toporov (DMT) was utilized to quantify the inter-particle adhesion force of both pure and surface modified fine aluminum powders (∼8 μm in size). Inverse Gas Chromatography was utilized for the determination of surface energy of the samples, and Atomic Force Microscopy was utilized to evaluate surface roughness of the powders. Surface modification of the original aluminum powders was done for the purpose of reduction in cohesiveness and improvement in flowability, employing either silane surface treatment or dry mechanical coating of nano-particles on the surface of original powders. For selected samples, the AFM was utilized for direct evaluation of the particle pull-off force. The results indicated that surface modification reduced the surface energy and altered the surface nano-roughness, resulting in drastic reduction of the inter-particle adhesion force. The particle bond number values were computed based on either the inter-particle adhesion force from the DMT model or the inter-particle pull-off force obtained from direct AFM measurements. Surface modification resulted in two to three fold reductions in the Bond number. In order to examine the influence of the particle scale property such as the Bond number on the bulk-scale flow characterization, Angle of Repose measurements were done and showed good qualitative agreements with the Bond number and acid/base surface characteristics of the powders. The results indicate a promising method that may be used to predict flow behavior of original (cohesive) and surface modified (previously cohesive) powders utilizing very small samples

Mps1 Phosphorylates Its N-Terminal Extension to Relieve Autoinhibition and Activate the Spindle Assembly Checkpoint

Monopolar spindle 1 (Mps1) is a conserved apical kinase in the spindle assembly checkpoint (SAC) that ensures accurate segregation of chromosomes during mitosis. Mps1 undergoes extensive auto- and transphosphorylation, but the regulatory and functional consequences of these modifications remain unclear. Recent findings highlight the importance of intermolecular interactions between the N-terminal extension (NTE) of Mps1 and the Hec1 subunit of the NDC80 complex, which control Mps1 localization at kinetochores and activation of the SAC. Whether the NTE regulates other mitotic functions of Mps1 remains unknown. Here, we report that phosphorylation within the NTE contributes to Mps1 activation through relief of catalytic autoinhibition that is mediated by the NTE itself. Moreover, we find that this regulatory NTE function is independent of its role in Mps1 kinetochore recruitment. We demonstrate that the NTE autoinhibitory mechanism impinges most strongly on Mps1-dependent SAC functions and propose that Mps1 activation likely occurs sequentially through dimerization of a “prone-to-autophosphorylate” Mps1 conformer followed by autophosphorylation of the NTE prior to maximal kinase activation segment trans-autophosphorylation. Our observations underline the importance of autoregulated Mps1 activity in generation and maintenance of a robust SAC in human cells

Blind testing cross-linking/mass spectrometry under the auspices of the 11th critical assessment of methods of protein structure prediction (CASP11)

Determining the structure of a protein by any method requires various contributions from experimental and computational sides. In a recent study, high-density cross-linking/mass spectrometry (HD-CLMS) data in combination with ab initio structure prediction determined the structure of human serum albumin (HSA) domains, with an RMSD to X-ray structure of up to 2.5 Å, or 3.4 Å in the context of blood serum. This paper reports the blind test on the readiness of this technology through the help of Critical Assessment of protein Structure Prediction (CASP). We identified between 201-381 unique residue pairs at an estimated 5% FDR (at link level albeit with missing site assignment precision evaluation), for four target proteins. HD-CLMS proved reliable once crystal structures were released. However, improvements in structure prediction using cross-link data were slight. We identified two reasons for this. Spread of cross-links along the protein sequence and the tightness of the spatial constraints must be improved. However, for the selected targets even ideal contact data derived from crystal structures did not allow modellers to arrive at the observed structure. Consequently, the progress of HD-CLMS in conjunction with computational modeling methods as a structure determination method, depends on advances on both arms of this hybrid approach

Two-Component Relativistic Hamiltonians and the Douglas-Kroll Approximation

The iterative solutions of the previously derived operator equation which defines an open-ended formalism for the reduction of the 4-component Dirac Hamiltonian to 2-component "electronic" operators of arbitrarily high accuracy, are discussed. It is shown that by departing from the approach based solely on the operator algebra one can define the initial iterative solution which leads to the 2-component Douglas-Kroll Hamiltonian. The present derivation reveals the origin of the success of methods based on the Douglas-Kroll Hamiltonian. It also shows that among relatively simple 2-component Hamiltonians, which are exact through the fourth power of the fine structure constant, the Douglas-Kroll operator is the most complete one. Also a computationally convenient and highly compact formula for matrix elements of the Douglas-Kroll Hamiltonian is obtained as a by-product of this investigation

A Comparison of Different Approximate Two-Component Relativistic Theories of Many-Electron Systems: A Case Study of the Ionization Energies of Two-Electron Ions

The corrections to the ionization energies of two-electron ions due to relativistic effects are studied by different two-component relativistic methods. In particular, the results obtained by the standard Pauli-Cowan-Griffin method and by two variants of the Douglas-Kroll-Hess method (the one based on the free-particle transformation and the one in which the transformation accounts for the nuclear potential) are compared with those calculated using the four-component Dirac-Fock method. Limits of applicability of each of these methods have been indicated. Results acceptable in the whole range of the nuclear charge (relativistic corrections accurate up to 4% for Z≤85) are given only by the Douglas-Kroll-Hess method which goes beyond the free-particle transformation. Each of the other two approaches either underestimates or overestimates the corrections due to relativistic effects