Machine learning recognition of protein secondary structures based on two-dimensional spectroscopic descriptors.

Protein secondary structure discrimination is crucial for understanding their biological function. It is not generally possible to invert spectroscopic data to yield the structure. We present a machine learning protocol which uses two-dimensional UV (2DUV) spectra as pattern recognition descriptors, aiming at automated protein secondary structure determination from spectroscopic features. Accurate secondary structure recognition is obtained for homologous (97%) and nonhomologous (91%) protein segments, randomly selected from simulated model datasets. The advantage of 2DUV descriptors over one-dimensional linear absorption and circular dichroism spectra lies in the cross-peak information that reflects interactions between local regions of the protein. Thanks to their ultrafast (∼200 fs) nature, 2DUV measurements can be used in the future to probe conformational variations in the course of protein dynamics.

Revealing the Critical Role of Global Electron Density Transfer in the Reaction Rate of Polar Organic Reactions within Molecular Electron Density Theory.

The critical role of global electron density transfer (GEDT) in increasing the reaction rate of polar organic reactions has been studied within the framework of Molecular Electron Density Theory (MEDT). To this end, the series of the polar Diels-Alder (P-DA) reactions of cyclopentadiene with cyanoethylene derivatives, for which experimental kinetic data are available, have been chosen. A complete linear correlation between the computed activation Gibbs free energies and the GEDT taking place at the polar transition state structures (TSs) is found; the higher the GEDT at the TS, the lower the activation Gibbs free energy. An interacting quantum atoms energy partitioning analysis allows for establishing a complete linear correlation between the electronic stabilization of the electrophilic ethylene frameworks and the GEDT taking place at the polar TSs. This finding supports Parr's proposal for the definition of the electrophilicity ω index. The present MEDT study establishes the critical role of the GEDT in the acceleration of polar reactions, since the electronic stabilization of the electrophilic framework with the electron density gain is greater than the destabilization of the nucleophilic one, making a net favorable electronic contribution to the decrease in the activation energy.

Structural elements regulating the photochromicity in a cyanobacteriochrome.

The three-dimensional (3D) crystal structures of the GAF3 domain of cyanobacteriochrome Slr1393 (Synechocystis PCC6803) carrying a phycocyanobilin chromophore could be solved in both 15-Z dark-adapted state, Pr, λmax = 649 nm, and 15-E photoproduct, Pg, λmax = 536 nm (resolution, 1.6 and 1.86 Å, respectively). The structural data allowed identifying the large spectral shift of the Pr-to-Pg conversion as resulting from an out-of-plane rotation of the chromophore's peripheral rings and an outward movement of a short helix formed from a formerly unstructured loop. In addition, a third structure (2.1-Å resolution) starting from the photoproduct crystals allowed identification of elements that regulate the absorption maxima. In this peculiar form, generated during X-ray exposition, protein and chromophore conformation still resemble the photoproduct state, except for the D-ring already in 15-Z configuration and tilted out of plane akin the dark state. Due to its formation from the photoproduct, it might be considered an early conformational change initiating the parental state-recovering photocycle. The high quality and the distinct features of the three forms allowed for applying quantum-chemical calculations in the framework of multiscale modeling to rationalize the absorption maxima changes. A systematic analysis of the PCB chromophore in the presence and absence of the protein environment showed that the direct electrostatic effect is negligible on the spectral tuning. However, the protein forces the outer pyrrole rings of the chromophore to deviate from coplanarity, which is identified as the dominating factor for the color regulation.

Tuning the Nucleophilicity and Electrophilicity of Group 10 Elements through Substituent Effects: A DFT Study.

In this study, a series of electron donor (-NH2, -NMe2 and -tBu) and electron-withdrawing substituents (-F, -CN and -NO2) were used to tune the nucleophilicity or electrophilicity of a series of square planar Ni2+, Pd2+ and Pt2+ malonate coordination complexes towards a pentafluoroiodobenzene and a pyridine molecule. In addition, Bader's theory of atoms in molecules (AIM), noncovalent interaction plot (NCIplot), molecular electrostatic potential (MEP) surface and natural bond orbital (NBO) analyses at the PBE0-D3/def2-TZVP level of theory were carried out to characterize and discriminate the role of the metal atom in the noncovalent complexes studied herein. We hope that the results reported herein may serve to expand the current knowledge regarding these metals in the fields of crystal engineering and supramolecular chemistry.

Spectroscopic Constants and Anharmonic Vibrational Frequencies of C(O)OC, c-C2O2 and Their Silicon-Containing Analogues.

Comets are likely to contain various carbon oxide molecules potentially including C(O)OC and c-C2O2 on their surfaces and comae, as well as their silicon-substituted analogues possibly playing a role in the formation of interstellar dust grains. In this work, high-level quantum chemical data are provided to support such potential future astrophysical detection through the generation of predicted rovibrational data. Laboratory-based chemistry would also benefit from such aforementioned computational benchmarking considering these molecules' historic computational and experimental elusiveness. Coupled-cluster singles, doubles, and perturbative triples, the F12b formalism, and the cc-pCVTZ-F12 basis set garner the rapid, yet highly trusted F12-TcCR level of theory leveraged presently. This current work points to all four molecules' strong IR activity, coupled with large intensities, thus suggesting the potential for JWST detection. Although Si(O)OSi possesses a permanent dipole moment significantly larger than those of the other molecules of present interest, the significant abundance of the potential precursor carbon monoxide suggests that the dicarbon dioxide molecules may yet be observable in the microwave region of the electromagnetic spectrum. Thus, this present work details the likely existence and detectability of these four cyclic molecules, providing updated implications compared to previous work performed both experimentally and computationally.

The Many Chemists Who Could Have Proposed the Woodward-Hoffmann Rules (Including Roald Hoffmann) But Didn't: The Theoretical and Physical Chemists†.

It is a reasonable question to ask, why, as of 1965 when the five Woodward-Hoffmann communication appeared, did no other physical chemist or chemical physicist or theoretical chemist discover the orbital symmetry rules for all pericyclic reactions? Two theoretical chemists - Luitzen Oosterhoff (in 1961) and Kenichi Fukui (in 1964) had discovered portions of the orbital symmetry rules; their stories appear in the papers immediately preceding this paper which is Paper 5 in a 27-paper series on the history of Woodward-Hoffmann rules. Concise yet telling stories of 19 other chemists who could have, might have, perhaps even should have discovered the Woodward-Hoffmann rules are presented with explanations as to why they did not do so. Social, political, and scientific explanations will summarize the analyses.

Why Hoffmann? His Chemistry.

Why was it that Roald Hoffmann was the perfect collaborator for R. B. Woodward for proposing the Principle of Conservation of Orbital Symmetry as the solution to the no-mechanism puzzle? This publication presents 17 "tools" that Hoffmann used extensively and effectively prior to the Woodward-Hoffmann collaboration that would he call upon reveal the mechanism of pericyclic reactions. In a sense, this is a biography of Hoffmann with a focus on his personal and professional skills as of May 5, 1964.

Why Hoffmann? The Person and the Young Chemical Physicist.

In 1965, R. B. Woodward and Roald Hoffmann published five communications that formed the basis of the Principle of Conservation of Orbital Symmetry which explained mechanisms of all pericyclic reactions and predicted the allowedness and forbiddeness of such reactions, whether thermal or photochemical. A brief biographical discussion of Hoffmann up to May 1964 is explains why Hoffmann was the ideal individual to participate in the collaboration with Woodward. Why May 1964? Because it was then that the Woodward-Hoffmann collaboration began.

Simulations of molecular photodynamics in long timescales.

Nonadiabatic dynamics simulations in the long timescale (much longer than 10 ps) are the next challenge in computational photochemistry. This paper delimits the scope of what we expect from methods to run such simulations: they should work in full nuclear dimensionality, be general enough to tackle any type of molecule and not require unrealistic computational resources. We examine the main methodological challenges we should venture to advance the field, including the computational costs of the electronic structure calculations, stability of the integration methods, accuracy of the nonadiabatic dynamics algorithms and software optimization. Based on simulations designed to shed light on each of these issues, we show how machine learning may be a crucial element for long time-scale dynamics, either as a surrogate for electronic structure calculations or aiding the parameterization of model Hamiltonians. We show that conventional methods for integrating classical equations should be adequate to extended simulations up to 1 ns and that surface hopping agrees semiquantitatively with wave packet propagation in the weak-coupling regime. We also describe our optimization of the Newton-X program to reduce computational overheads in data processing and storage. This article is part of the theme issue 'Chemistry without the Born-Oppenheimer approximation'.

Electronic Structure and Solvation Effects from Core and Valence Photoelectron Spectroscopy of Serum Albumin.

X-ray photoelectron spectroscopy of bovine serum albumin (BSA) in a liquid jet is used to investigate the electronic structure of a solvated protein, yielding insight into charge transfer mechanisms in biological systems in their natural environment. No structural damage was observed in BSA following X-ray photoelectron spectroscopy in a liquid jet sample environment. Carbon and nitrogen atoms in different chemical environments were resolved in the X-ray photoelectron spectra of both solid and solvated BSA. The calculations of charge distributions demonstrate the difficulty of assigning chemical contributions in complex systems in an aqueous environment. The high-resolution X-ray core electron spectra recorded are unchanged upon solvation. A comparison of the valence bands of BSA in both phases is also presented. These bands display a higher sensitivity to solvation effects. The ionization energy of the solvated BSA is determined at 5.7 ± 0.3 eV. Experimental results are compared with theoretical calculations to distinguish the contributions of various molecular components to the electronic structure. This comparison points towards the role of water in hole delocalization in proteins.

Continuum Electronic States: The Tiresia Code.

A multicenter (LCAO) B-spline basis is described in detail, and its capabilities concerning affording convergent solutions for electronic continuum states and wavepacket propagation are presented. It forms the core of the Tiresia code, which implements static-DFT and TDDFT hamiltonians, as well as single channel Dyson-DFT and Dyson-TDDFT descriptions to include correlation in the bound states. Together they afford accurate and computationally efficient descriptions of photoionization properties of complex systems, both in the single photon and strong field environments. A number of examples are provided.

A Simplified Treatment for Efficiently Modeling the Spectral Signal of Vibronic Transitions: Application to Aqueous Indole.

In this paper, we introduce specific approximations to simplify the vibronic treatment in modeling absorption and emission spectra, allowing us to include a huge number of vibronic transitions in the calculations. Implementation of such a simplified vibronic treatment within our general approach for modelling vibronic spectra, based on molecular dynamics simulations and the perturbed matrix method, provided a quantitative reproduction of the absorption and emission spectra of aqueous indole with higher accuracy than the one obtained when using the existing vibronic treatment. Such results, showing the reliability of the approximations employed, indicate that the proposed method can be a very efficient and accurate tool for computational spectroscopy.

IOData: A python library for reading, writing, and converting computational chemistry file formats and generating input files.

IOData is a free and open-source Python library for parsing, storing, and converting various file formats commonly used by quantum chemistry, molecular dynamics, and plane-wave density-functional-theory software programs. In addition, IOData supports a flexible framework for generating input files for various software packages. While designed and released for stand-alone use, its original purpose was to facilitate the interoperability of various modules in the HORTON and ChemTools software packages with external (third-party) molecular quantum chemistry and solid-state density-functional-theory packages. IOData is designed to be easy to use, maintain, and extend; this is why we wrote IOData in Python and adopted many principles of modern software development, including comprehensive documentation, extensive testing, continuous integration/delivery protocols, and package management. This article is the official release note of the IOData library.

A Statistically Supported Antioxidant Activity DFT Benchmark-The Effects of Hartree-Fock Exchange and Basis Set Selection on Accuracy and Resources Uptake.

Polyphenolic compounds are now widely studied using computational chemistry approaches, the most popular of which is Density Functional Theory. To ease this process, it is critical to identify the optimal level of theory in terms of both accuracy and resource usage-a challenge we tackle in this study. Eleven DFT functionals with varied Hartree-Fock exchange values, both global and range-separated hybrids, were combined with 14 differently augmented basis sets to calculate the reactivity indices of caffeic acid, a phenolic acid representative, and compare them to experimental data or a high-level of theory outcome. Aside from the main course, a validation of the widely used Janak's theorem in the establishment of vertical ionization potential and vertical electron affinity was evaluated. To investigate what influences the values of the properties under consideration, linear regression models were developed and thoroughly discussed. The results were utilized to compute the scores, which let us determine the best and worst combinations and make broad suggestions on the final option. The study demonstrates that M06-2X/6-311G(d,p) is the best fit for such research, and, curiously, it is not necessarily essential to include a diffuse function to produce satisfactory results.

Quantitative and Chemically Intuitive Evaluation of the Nature of M-L Bonds in Paramagnetic Compounds: Application of EDA-NOCV Theory to Spin Crossover Complexes.

To improve understanding of M-L bonds in 3d transition metal complexes, analysis by energy decomposition analysis and natural orbital for chemical valence model (EDA-NOCV) is desirable as it provides a full, quantitative and chemically intuitive ab initio description of the M-L interactions. In this study, a generally applicable fragmentation and computational protocol was established and validated by using octahedral spin crossover (SCO) complexes, as the transition temperature (T1/2 ) is sensitive to subtle changes in M-L bonding. Specifically, EDA-NOCV analysis of Fe-N bonds in five [FeII (Lazine )2 (NCBH3 )2 ], in both low-spin (LS) and paramagnetic high-spin (HS) states led to: 1) development of a general, widely applicable, corrected M+L6 fragmentation, tested against a family of five LS [FeII (Lazine )3 ](BF4 )2 complexes; this confirmed that three Lazine are stronger ligands (ΔEorb,σ+π =-370 kcal mol-1 ) than 2 Lazine +2 NCBH3 (=-335 kcal mol-1 ), as observed. 2) Analysis of Fe-L bonding on LS→HS, reveals more ionic (ΔEelstat ) and less covalent (ΔEorb ) character (ΔEelstat :ΔEorb 55:45 LS→64:36 HS), mostly due to a big drop in σ (ΔEorb,σ ↓50 %; -310→-145 kcal mol-1 ), and a drop in π contributions (ΔEorb,π ↓90 %; -30→-3 kcal mol-1 ). 3) Strong correlation of observed T1/2 and ΔEorb,σ+π , for both LS and HS families (R2 =0.99 LS, R2 =0.95 HS), but no correlation of T1/2 and ΔΔEorb,σ+π (LS-HS) (R2 =0.11). Overall, this study has established and validated an EDA-NOCV protocol for M-L bonding analysis of any diamagnetic or paramagnetic, homoleptic or heteroleptic, octahedral transition metal complex. This new and widely applicable EDA-NOCV protocol holds great promise as a predictive tool.

Embedding a Planar Hypercoordinate Carbon Atom into a [4n+2] π-System.

Through delicate tuning of the electronic structure, we report herein a rational design of seventeen new putative global minimum energy structures containing a planar tetra- or pentacoordinate carbon atom embedded in an aromatic hydrocarbon. These structures are the result of replacing three consecutive hydrogen atoms of an aromatic hydrocarbon by less electronegative groups, forming a multicenter σ-bond with the planar hypercoordinate carbon atom and participating in the π-electron delocalization. This strategy that maximizes both mechanical and electronic effects through aromatic architectures can be extended to several molecular combinations to achieve new and diverse compounds containing planar hypercoordinate carbon centers.

d-d Dative Bonding Between Iron and the Alkaline-Earth Metals Calcium, Strontium, and Barium.

Double deprotonation of the diamine 1,1'-(tBuCH2 NH)-ferrocene (1-H2 ) by alkaline-earth (Ae) or EuII metal reagents gave the complexes 1-Ae (Ae=Mg, Ca, Sr, Ba) and 1-Eu. 1-Mg crystallized as a monomer while the heavier complexes crystallized as dimers. The Fe⋅⋅⋅Mg distance in 1-Mg is too long for a bonding interaction, but short Fe⋅⋅⋅Ae distances in 1-Ca, 1-Sr, and 1-Ba clearly support intramolecular Fe⋅⋅⋅Ae bonding. Further evidence for interactions is provided by a tilting of the Cp rings and the related 1 H NMR chemical-shift difference between the Cp α and ß protons. While electrochemical studies are complicated by complex decomposition, UV/Vis spectral features of the complexes support Fe→Ae dative bonding. A comprehensive bonding analysis of all 1-Ae complexes shows that the heavier species 1-Ca, 1-Sr, and 1-Ba possess genuine Fe→Ae bonds which involve vacant d-orbitals of the alkaline-earth atoms and partially filled d-orbitals on Fe. In 1-Mg, a weak Fe→Mg donation into vacant p-orbitals of the Mg atom is observed.

Proline autocatalysis in the origin of biological enantioenriched chirality.

Biological enantioenriched chirality is a phenomenon that in living organisms, amino acids and carbohydrates typically have the same absolute configuration. Perhaps one of the earliest attempts to delineate the origins of this phenomenon was a theory known as asymmetric autocatalysis, a reaction in which the structures of the chiral catalyst and the product are the same, and in which the chiral product acts as a chiral catalyst for its own production. In theory, this would mean that small asymmetries in the product will propagate rapidly. However, autocatalysis also relies on the cross-inhibition of chiral states, something that would not likely be possible on primordial Earth. But recently, theories on asymmetric autocatalysis have begun to resurface as more recent findings indicate that other mechanisms exist to stabilize the homochiral states. In this study, I propose an autocatalytic cycle, and using density functional theory, prove that (1) it is plausible on primordial Earth, and (2) it propagates arbitrary asymmetries in proline. Thus, facilitating asymmetry in proline and allowing access to a wide variety of asymmetric proline-catalyzed reactions, including those involved in the synthesis of amino acids and carbohydrates from achiral precursors.

Theoretical Estimation of Optimal Parameters for Maximum Fluorescence under Pulsed Excitation.

We present a detailed theoretical study on choosing optimum excitation parameters for maximizing the fluorescence yield. Using a model system, we show how the time-averaged emission (fluorescence) is modulated as the excitation conditions are changed from continuous wave excitation to pulsed excitation with various combinations of pulse widths and pulse repetition-rates for the same time-averaged excitation intensity. We conclude that depending on the excitation intensity, different pulse parameters are required for generating maximum fluorescence output. Our method can be implemented for other more sophisticated models without much difficulty.