Interoperable workflows by exchanging grid-based data between quantum-chemical program packages.

Quantum-chemical subsystem and embedding methods require complex workflows that may involve multiple quantum-chemical program packages. Moreover, such workflows require the exchange of voluminous data that go beyond simple quantities, such as molecular structures and energies. Here, we describe our approach for addressing this interoperability challenge by exchanging electron densities and embedding potentials as grid-based data. We describe the approach that we have implemented to this end in a dedicated code, PyEmbed, currently part of a Python scripting framework. We discuss how it has facilitated the development of quantum-chemical subsystem and embedding methods and highlight several applications that have been enabled by PyEmbed, including wave-function theory (WFT) in density-functional theory (DFT) embedding schemes mixing non-relativistic and relativistic electronic structure methods, real-time time-dependent DFT-in-DFT approaches, the density-based many-body expansion, and workflows including real-space data analysis and visualization. Our approach demonstrates, in particular, the merits of exchanging (complex) grid-based data and, in general, the potential of modular software development in quantum chemistry, which hinges upon libraries that facilitate interoperability.

Structural Dependence of Extended Amide III Vibrations in Two-Dimensional Infrared Spectra.

Two-dimensional infrared (2D-IR) spectroscopy is a powerful experimental method for probing the structure and dynamics of proteins in aqueous solution. So far, most experimental studies have focused on the amide I vibrations, for which empirical vibrational exciton models provide a means of interpreting such experiments. However, such models are largely lacking for other regions of the vibrational spectrum. To close this gap, we employ an efficient quantum-chemical methodology for the calculation of 2D-IR spectra, which is based on anharmonic theoretical vibrational spectroscopy with localized modes. We apply this approach to explore the potential of 2D-IR spectroscopy in the extended amide III region. Using calculations for a dipeptide model as well as alanine polypeptides, we show that distinct 2D-IR cross-peaks in the extended amide III region can potentially be used to distinguish α-helix and ß-strand structures. We propose that the extended amide III region could be a promising target for future 2D-IR experiments.

A simple and consistent quantum-chemical fragmentation scheme for proteins that includes two-body contributions.

The Molecular Fractionation with Conjugate Caps (MFCC) method is a popular fragmentation method for the quantum-chemical treatment of proteins. However, it does not account for interactions between the amino acid fragments, such as intramolecular hydrogen bonding. Here, we present a combination of the MFCC fragmentation scheme with a second-order many-body expansion (MBE) that consistently accounts for all fragment-fragment, fragment-cap, and cap-cap interactions, while retaining the overall simplicity of the MFCC scheme with its chemically meaningful fragments. We show that with the resulting MFCC-MBE(2) scheme, the errors in the total energies of selected polypeptides and proteins can be reduced by up to one order of magnitude and relative energies of different protein conformers can be predicted accurately.

Quantum-chemical calculation of two-dimensional infrared spectra using localized-mode VSCF/VCI.

Computational protocols for the simulation of two-dimensional infrared (2D IR) spectroscopy usually rely on vibrational exciton models which require an empirical parameterization. Here, we present an efficient quantum-chemical protocol for predicting static 2D IR spectra that does not require any empirical parameters. For the calculation of anharmonic vibrational energy levels and transition dipole moments, we employ the localized-mode vibrational self-consistent field (L-VSCF)/vibrational configuration interaction (L-VCI) approach previously established for (linear) anharmonic theoretical vibrational spectroscopy [P. T. Panek and C. R. Jacob, ChemPhysChem 15, 3365-3377 (2014)]. We demonstrate that with an efficient expansion of the potential energy surface using anharmonic one-mode potentials and harmonic two-mode potentials, 2D IR spectra of metal carbonyl complexes and dipeptides can be predicted reliably. We further show how the close connection between L-VCI and vibrational exciton models can be exploited to extract the parameters of such models from those calculations. This provides a novel route to the fully quantum-chemical parameterization of vibrational exciton models for predicting 2D IR spectra.

Accurate quantum-chemical fragmentation calculations for ion-water clusters with the density-based many-body expansion.

The many-body expansion (MBE) provides an attractive fragmentation method for the efficient quantum-chemical treatment of molecular clusters. However, its convergence with the many-body order is generally slow for molecular clusters that exhibit large intermolecular polarization effects. Ion-water clusters are thus a particularly challenging test case for quantum-chemical fragmentation methods based on the MBE. Here, we assess the accuracy of both the conventional, energy-based MBE and the recently developed density-based MBE [Schmitt-Monreal and Jacob, Int. J. Quantum Chem., 2020, 120, e26228] for ion-water clusters. As test cases, we consider hydrated Ca2+, F-, OH-, and H3O+, and compare both total interaction energies and the relative interaction energies of different structural isomers. We show that an embedded density-based two-body expansion yields highly accurate results compared to supermolecular calculations. Already at the two-body level, the density-based MBE clearly outperforms a conventional, energy-based embedded three-body expansion. We compare different embedding schemes and find that a relaxed frozen-density embedding potential yields the most accurate results. This opens the door to accurate and efficient quantum-chemical calculations for large ion-water clusters as well as condensed-phase systems.

Systematic Partitioning of Proteins for Quantum-Chemical Fragmentation Methods Using Graph Algorithms.

Quantum-chemical fragmentation methods offer an efficient approach for the treatment of large proteins, in particular if local target quantities such as protein-ligand interaction energies, enzymatic reaction energies, or spectroscopic properties of embedded chromophores are sought. However, the accuracy that is achievable for such local target quantities intricately depends on how the protein is partitioned into smaller fragments. While the commonly employed naïve approach of using fragments with a fixed size is widely used, it can result in large and unpredictable errors when varying the fragment size. Here, we present a systematic partitioning scheme that aims at minimizing the fragmentation error of a local target quantity for a given maximum fragment size. To this end, we construct a weighted graph representation of the protein, in which the amino acids constitute the nodes. These nodes are connected by edges weighted with an estimate for the fragmentation error that is expected when cutting this edge. This allows us to employ graph partitioning algorithms provided by computer science to determine near-optimal partitions of the protein. We apply this scheme to a test set of six proteins representing various prototypical applications of quantum-chemical fragmentation methods using a simplified molecular fractionation with conjugate caps (MFCC) approach with hydrogen caps. We show that our graph-based scheme consistently improves upon the naïve approach.

A new ultrafast energy funneling material harvests three times more diffusive solar energy for GaInP photovoltaics.

There is no theoretical limit in using molecular networks to harvest diffusive sun photons on large areas and funnel them onto much smaller areas of highly efficient but also precious energy-converting materials. The most effective concept reported so far is based on a pool of randomly oriented, light-harvesting donor molecules that funnel all excitation quanta by ultrafast energy transfer to individual light-redirecting acceptor molecules oriented parallel to the energy converters. However, the best practical light-harvesting system could only be discovered by empirical screening of molecules that either align or not within stretched polymers and the maximum absorption wavelength of the empirical system was far away from the solar maximum. No molecular property was known explaining why certain molecules would align very effectively whereas similar molecules did not. Here, we first explore what molecular properties are responsible for a molecule to be aligned. We found a parameter derived directly from the molecular structure with a high predictive power for the alignability. In addition, we found a set of ultrafast funneling molecules that harvest three times more energy in the solar's spectrum peak for GaInP photovoltaics. A detailed study on the ultrafast dipole moment reorientation dynamics demonstrates that refocusing of the diffusive light is based on ∼15-ps initial dipole moment depolarization followed by ∼50-ps repolarization into desired directions. This provides a detailed understanding of the molecular depolarization/repolarization processes responsible for refocusing diffusively scattered photons without violating the second law of thermodynamics.

Position 123 of halohydrin dehalogenase HheG plays an important role in stability, activity, and enantioselectivity.

HheG from Ilumatobacter coccineus is a halohydrin dehalogenase with synthetically useful activity in the ring opening of cyclic epoxides with various small anionic nucleophiles. This enzyme provides access to chiral ß-substituted alcohols that serve as building blocks in the pharmaceutical industry. Wild-type HheG suffers from low thermostability, which poses a significant drawback for potential applications. In an attempt to thermostabilize HheG by protein engineering, several single mutants at position 123 were identified which displayed up to 14 °C increased apparent melting temperatures and up to three-fold higher activity. Aromatic amino acids at position 123 resulted even in a slightly higher enantioselectivity. Crystal structures of variants T123W and T123G revealed a flexible loop opposite to amino acid 123. In variant T123G, this loop adopted two different positions resulting in an open or partially closed active site. Classical molecular dynamics simulations confirmed a high mobility of this loop. Moreover, in variant T123G this loop adopted a position much closer to residue 123 resulting in denser packing and increased buried surface area. Our results indicate an important role for position 123 in HheG and give first structural and mechanistic insight into the thermostabilizing effect of mutations T123W and T123G.

Microsecond Simulation of Electron Transfer in DNA: Bottom-Up Parametrization of an Efficient Electron Transfer Model Based on Atomistic Details.

The transfer of electrons over long distances in complex molecular systems is a phenomenon of significance in both biochemistry and technology. In recent years, we have been developing efficient models to study ET in complex systems, including DNA as a prominent example. Ab initio and model approaches have been combined in an "on-the-fly" calculation of ET parameters, which can be used to propagate nuclear and electronic degrees of freedom simultaneously. These previous efforts have aimed at deriving an efficient nonadiabatic quantum mechanical-molecular mechanical (QM/MM) simulation scheme for ET, making nanosecond simulations of ET in realistic systems possible. This, however, is still insufficient for the treatment of large donor-bridge-acceptor systems, like the ET in DNA, overcoming long adenine bridges. Therefore, we have constructed a theoretical model in a bottom-up manner. All quantum-chemical as well as force-field calculations are substituted by theoretical models of the involved phenomena on a molecular level, including polarization and relaxation of the molecular environment, which are often omitted in other recently developed theoretical models of ET. A nonadiabatic simulation scheme is employed, and no assumptions regarding the ET mechanism are needed. Thus, the predictive power of the simulations is preserved, while pushing the limits of the accessible time scales beyond microseconds. This model-based simulation scheme is applied to ET in various DNA species. Good agreement with the "full" atomistic nonadiabatic QM/MM scheme is observed for the archetypal DNA ET systems, the polyA sequence, as well as the sequences GTnGGG, containing adenines as bridge sites. Furthermore, ET in larger, more complex DNA sequences is simulated, and the results are discussed.

Charge transport in desolvated DNA.

The conductivity of DNA in molecular junctions is often probed experimentally under dry conditions, but it is unclear how much of the solvent remains attached to the DNA and how this impacts its structure, electronic states, and conductivity. Classical MD simulations show that DNA is unstable if the solvent is removed completely, while a micro-hydrated system with few water molecules shows similar charge transport properties as fully solvated DNA does. This surprising effect is analyzed in detail by mapping the density functional theory-based electronic structure to a tight-binding Hamiltonian, allowing for an estimate of conductivity of various DNA sequences with snapshot-averaged Landauer's approach. The characteristics of DNA charge transport turn out to be determined by the nearest hydration shell(s), and the removal of bulk solvent has little effect on the transport.

On the structure and stretching of microhydrated DNA.

The structure of short double-stranded DNA oligomers in complex with varied amounts of water is investigated with classical molecular dynamics. Free simulations are performed first and mechanical stress is switched on afterward, resembling the conditions of single-molecule conductivity experiments. Water as well as counterions are seen to contribute to the stabilization of double-stranded DNA structure, and a collapse of the native DNA structure is observed upon the removal of a certain amount of water. Pulling with a moderate external force provides additional support to the double-stranded DNA structure, whereas larger forces lead to the overstretching transition followed by the separation of DNA strands, in a manner similar to that observed in fully hydrated DNA.