Extracting the electronic structure signal from X-ray and electron scattering in the gas phase.

X-ray and electron scattering from free gas-phase molecules is examined using the independent atom model (IAM) and ab initio electronic structure calculations. The IAM describes the effect of the molecular geometry on the scattering, but does not account for the redistribution of valence electrons due to, for instance, chemical bonding. By examining the total, i.e. energy-integrated, scattering from three molecules, fluoroform (CHF3), 1,3-cyclohexadiene (C6H8) and naphthalene (C10H8), the effect of electron redistribution is found to predominantly reside at small-to-medium values of the momentum transfer (q ≤ 8 Å-1) in the scattering signal, with a maximum percent difference contribution at 2 ≤ q ≤ 3 Å-1. A procedure to determine the molecular geometry from the large-q scattering is demonstrated, making it possible to more clearly identify the deviation of the scattering from the IAM approximation at small and intermediate q and to provide a measure of the effect of valence electronic structure on the scattering signal.

The Ring-Closing Reaction of Cyclopentadiene Probed with Ultrafast X-ray Scattering.

The dynamics of cyclopentadiene (CP) following optical excitation at 243 nm was investigated by time-resolved pump-probe X-ray scattering using 16.2 keV X-rays at the Linac Coherent Light Source (LCLS). We present the first ultrafast structural evidence that the reaction leads directly to the formation of bicyclo[2.1.0]pentene (BP), a strained molecule with three- and four-membered rings. The bicyclic compound decays via a thermal backreaction to the vibrationally hot CP with a time constant of 21 ± 3 ps. A minor channel leads to ring-opened structures on a subpicosecond time scale.

IntPred: a structure-based predictor of protein-protein interaction sites.

MOTIVATION: Protein-protein interactions are vital for protein function with the average protein having between three and ten interacting partners. Knowledge of precise protein-protein interfaces comes from crystal structures deposited in the Protein Data Bank (PDB), but only 50% of structures in the PDB are complexes. There is therefore a need to predict protein-protein interfaces in silico and various methods for this purpose. Here we explore the use of a predictor based on structural features and which exploits random forest machine learning, comparing its performance with a number of popular established methods. RESULTS: On an independent test set of obligate and transient complexes, our IntPred predictor performs well (MCC = 0.370, ACC = 0.811, SPEC = 0.916, SENS = 0.411) and compares favourably with other methods. Overall, IntPred ranks second of six methods tested with SPPIDER having slightly better overall performance (MCC = 0.410, ACC = 0.759, SPEC = 0.783, SENS = 0.676), but considerably worse specificity than IntPred. As with SPPIDER, using an independent test set of obligate complexes enhanced performance (MCC = 0.381) while performance is somewhat reduced on a dataset of transient complexes (MCC = 0.303). The trade-off between sensitivity and specificity compared with SPPIDER suggests that the choice of the appropriate tool is application-dependent. AVAILABILITY AND IMPLEMENTATION: IntPred is implemented in Perl and may be downloaded for local use or run via a web server at www.bioinf.org.uk/intpred/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Ab Initio Fragment Method for Calculating Molecular X-ray Diffraction.

A fragment-based approach for the prediction of elastic X-ray scattering is presented. The total diffraction pattern is assembled from anisotropic form factors calculated for individual molecular fragments, optionally including corrections for pairwise interactions between fragments. The approach is evaluated against full ab initio scattering calculations in the peptide diphenylalanine, and the optimal selection of fragments is examined in the ethanol molecule. The approach is found to improve significantly on the independent atom model while remaining conceptually simple and computationally efficient. It is expected to be particularly useful for macromolecules with repeated subunits, such as peptides, proteins, DNA, or RNA and other polymers, where it is straightforward to define appropriate fragments.

Imaging rotations and vibrations in polyatomic molecules with X-ray scattering.

An approach for calculating elastic X-ray scattering from polyatomic molecules in specific electronic, vibrational, and rotational states is presented, and is used to consider the characterization of specific states in polyatomic molecules using elastic X-ray scattering. Instead of the standard independent atom model (IAM) method, the X-ray scattering is calculated directly from ab initio wavefunctions. The role of molecular symmetry and Friedel's law is examined, with the molecules BF3, C5H5-, NF3, and 1,3-cyclohexadiene used as specific examples. The contributions to the elastic X-ray scattering from the electronic, vibrational, and rotational portions of the molecular wavefunction are examined in CS2. In particular, it is observed that the rotational states give rise to distinct signatures in the scattering signal.

Elastic X-ray scattering from state-selected molecules.

The characterization of electronic, vibrational, and rotational states using elastic (coherent) X-ray scattering is considered. The scattering is calculated directly from complete active space self-consistent field level ab initio wavefunctions for H2 molecules in the ground-state X1Σg+ and first-excited EF1Σg+ electronic states. The calculated scattering is compared to recent experimental measurements [Y.-W. Liu et al., Phys. Rev. A 89, 014502 (2014)], and the influence of vibrational and rotational states on the observed signal is examined. The scaling of the scattering calculations with basis set is quantified, and it is found that energy convergence of the ab initio calculations is a good indicator of the quality of the scattering calculations.

Tracking multiple components of a nuclear wavepacket in photoexcited Cu(I)-phenanthroline complex using ultrafast X-ray spectroscopy.

Disentangling the strong interplay between electronic and nuclear degrees of freedom is essential to achieve a full understanding of excited state processes during ultrafast nonadiabatic chemical reactions. However, the complexity of multi-dimensional potential energy surfaces means that this remains challenging. The energy flow during vibrational and electronic relaxation processes can be explored with structural sensitivity by probing a nuclear wavepacket using femtosecond time-resolved X-ray Absorption Near Edge Structure (TR-XANES). However, it remains unknown to what level of detail vibrational motions are observable in this X-ray technique. Herein we track the wavepacket dynamics of a prototypical [Cu(2,9-dimethyl-1,10-phenanthroline)2]+ complex using TR-XANES. We demonstrate that sensitivity to individual wavepacket components can be modulated by the probe energy and that the bond length change associated with molecular breathing mode can be tracked with a sub-Angstrom resolution beyond optical-domain observables. Importantly, our results reveal how state-of-the-art TR-XANES provides deeper insights of ultrafast nonadiabatic chemical reactions.

Regio- and conformational isomerization critical to design of efficient thermally-activated delayed fluorescence emitters.

Regio- and conformational isomerization are fundamental in chemistry, with profound effects upon physical properties, however their role in excited state properties is less developed. Here two regioisomers of bis(10H-phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S-dioxide, a donor-acceptor-donor (D-A-D) thermally-activated delayed fluorescence (TADF) emitter, are studied. 2,8-bis(10H-phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S-dioxide exhibits only one quasi-equatorial conformer on both donor sites, with charge-transfer (CT) emission close to the local triplet state leading to efficient TADF via spin-vibronic coupling. However, 3,7-bis(10H-phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S-dioxide displays both a quasi-equatorial CT state and a higher-energy quasi-axial CT state. No TADF is observed in the quasi-axial CT emission. These two CT states link directly to the two folded conformers of phenothiazine. The presence of the low-lying local triplet state of the axial conformer also means that this quasi-axial CT is an effective loss pathway both photophysically and in devices. Importantly, donors or acceptors with more than one conformer have negative repercussions for TADF in organic light-emitting diodes.

Conformational dynamics and aggregation behavior of piezoelectric diphenylalanine peptides in an external electric field.

Aromatic peptides including diphenylalanine (FF) have the capacity to self-assemble into ordered, biocompatible nanostructures with piezoelectric properties relevant to a variety of biomedical applications. Electric fields are commonly applied to align FF nanotubes, yet little is known about the effect of the electric field on the assembly process. Using all-atom molecular dynamics with explicit water molecules, we examine the response of FF monomers to the application of a constant external electric field over a range of intensities. We probe the aggregation mechanism of FF peptides, and find that the presence of even relatively weak fields can accelerate ordered aggregation, primarily by facilitating the alignment of individual molecular dipole moments. This is modulated by the conformational response of individual FF peptides (e.g., backbone stretching) and by the cooperative alignment of neighboring FF and water molecules. These observations may facilitate future studies on the controlled formation of nanostructured aggregates of piezoelectric peptides and the understanding of their electro-mechanical properties.

Ab Initio Calculation of Molecular Diffraction.

We discuss the application of ab initio X-ray diffraction (AIXRD) to the interpretation of time-resolved and static X-ray diffraction. In our approach, elastic X-ray scattering is calculated directly from the ab initio multiconfigurational wave function via a Fourier transform of the electron density, using the first Born approximation for elastic scattering. Significant gains in efficiency can be obtained by performing the required Fourier transforms analytically, making it possible to combine the calculation of ab initio X-ray diffraction with expensive quantum dynamics simulations. We show that time-resolved X-ray diffraction can detect not only changes in molecular geometry but also changes in the electronic state of a molecule. Calculations for cis-, trans-, and cyclo-butadiene, as well as benzene and 1,3-cyclohexadiene are included.

Toward structural femtosecond chemical dynamics: imaging chemistry in space and time.

We aim to observe a chemical reaction in real time using gas-phase X-ray diffraction. In our initial experiment at the Linac Coherent Light Source (LCLS), we investigated the model system 1,3-cyclohexadiene (CHD) at very low vapor pressures. This reaction serves as a benchmark for numerous transformations in organic synthesis and natural product biology. Excitation of CHD by an ultraviolet optical pulse initiates an electrocyclic reaction that transforms the closed ring system into the open-chain structure of 1,3,5-hexatriene. We describe technical points of the experimental method and present first results. We also outline an approach to analyze the data involving nonlinear least-square optimization routines that match the experimental observations with predicted diffraction patterns calculated from trajectories for nonadiabatic vibronic wave packets.