Tailored and Externally Corrected Coupled Cluster with Quantum Inputs.

We propose to use wave function overlaps obtained from a quantum computer as inputs for the classical split-amplitude techniques, tailored and externally corrected coupled cluster, to achieve balanced treatment of static and dynamic correlation effects in molecular electronic structure simulations. By combining insights from statistical properties of matchgate shadows, which are used to measure quantum trial state overlaps, with classical correlation diagnostics, we can provide quantum resource estimates well into the classically no longer exactly solvable regime. We find that rather imperfect wave functions and remarkably low shot counts are sufficient to cure qualitative failures of plain coupled cluster singles doubles and to obtain chemically precise dynamic correlation energy corrections. We provide insights into which wave function preparation schemes have a chance of yielding quantum advantage, and we test our proposed method using overlaps measured on Google's Sycamore device.

responsefun: Fun with Response Functions in the Algebraic Diagrammatic Construction Framework.

We present the open-source responsefun package, which implements a universally applicable procedure for computing molecular response properties within the algebraic diagrammatic construction (ADC) framework, exploiting the intermediate state representation (ISR) approach. With symbolic mathematics, the user can simply enter textbook sum-over-states (SOS) expressions from time-dependent perturbation theory, which are then automatically translated into the corresponding symbolic ADC/ISR formulations. Using the data structures provided by the hybrid Python/C++ module adcc for calculating excited states with ADC, the specified response property is directly evaluated, and the result is returned to the user. Employing the novel responsefun package, we present the first ADC/ISR calculations of second-order hyperpolarizability tensors and three-photon-absorption matrix elements.

Solving response expressions in the ADC/ISR framework.

We present an implementation for the calculation of molecular response properties using the algebraic-diagrammatic construction (ADC)/intermediate state representation approach. For the second-order ADC model [ADC(2)], a memory-efficient ansatz avoiding the storage of double excitation amplitudes is investigated. We compare the performance of different numerical algorithms for the solution of the underlying response equations for ADC(2) and show that our approach also strongly improves the convergence behavior for the investigated algorithms compared with the standard implementation. All routines are implemented in an open-source Python library.

Efficient quantum analytic nuclear gradients with double factorization.

Efficient representations of the Hamiltonian, such as double factorization, drastically reduce the circuit depth or the number of repetitions in error corrected and noisy intermediate-scale quantum (NISQ) algorithms for chemistry. We report a Lagrangian-based approach for evaluating relaxed one- and two-particle reduced density matrices from double factorized Hamiltonians, unlocking efficiency improvements in computing the nuclear gradient and related derivative properties. We demonstrate the accuracy and feasibility of our Lagrangian-based approach to recover all off-diagonal density matrix elements in classically simulated examples with up to 327 quantum and 18 470 total atoms in QM/MM simulations with modest-sized quantum active spaces. We show this in the context of the variational quantum eigensolver in case studies, such as transition state optimization, ab initio molecular dynamics simulation, and energy minimization of large molecular systems.

Magnetic circular dichroism within the algebraic diagrammatic construction scheme of the polarization propagator up to third order.

We present an implementation of the B term of Magnetic Circular Dichroism (MCD) within the Algebraic Diagrammatic Construction (ADC) scheme of the polarization propagator and its Intermediate State Representation. As illustrative results, the MCD spectra of the ADC variants ADC(2), ADC(2)-x, and ADC(3) of the molecular systems uracil, 2-thiouracil, 4-thiouracil, purine, hypoxanthine 1,4-naphthoquinone, 9,10-anthraquinone, and 1-naphthylamine are computed and compared with results obtained by using the Resolution-of-Identity Coupled-Cluster Singles and Approximate Doubles method, with literature Time-Dependent Density Functional Theory results, and with available experimental data.

A long-lived fluorenyl cation: efficiency booster for uncaging and photobase properties.

The photochemistry of fluorenols has been of special interest for many years. This is because both the fluorenol and the fluorenyl cation are antiaromatic in the ground state due to their 4n π-electrons according to the Hückel rule. The photolysis reaction of various fluorene derivatives takes place via a cation intermediate and is preferred due to its excited state aromaticity. Here we present an extremely long-lived fluorenyl cation and its effects on the uncaging of various leaving groups. We analyze the relationship between uncaging quantum yields of fluorene-based cages and the longevity of their fluorenyl cations with different spectroscopic methods in the steady state and on an ultrafast time scale and find that the uncaging quantum yield rises with the stability of the cation. In contrast to previous reports, the cation can be observed on a time scale of minutes, even in moderately protic solvents as methanol and ethanol. The stability of this cation depends on the dimethylamino-substituents on the fluorene scaffold and the properties of the solvent. In addition, with bis-dimethylamino fluorenol, a photobase is introduced that expands the small group of known photoinduced hydroxide emitters.

Quantum Chemistry Common Driver and Databases (QCDB) and Quantum Chemistry Engine (QCEngine): Automation and interoperability among computational chemistry programs.

Community efforts in the computational molecular sciences (CMS) are evolving toward modular, open, and interoperable interfaces that work with existing community codes to provide more functionality and composability than could be achieved with a single program. The Quantum Chemistry Common Driver and Databases (QCDB) project provides such capability through an application programming interface (API) that facilitates interoperability across multiple quantum chemistry software packages. In tandem with the Molecular Sciences Software Institute and their Quantum Chemistry Archive ecosystem, the unique functionalities of several CMS programs are integrated, including CFOUR, GAMESS, NWChem, OpenMM, Psi4, Qcore, TeraChem, and Turbomole, to provide common computational functions, i.e., energy, gradient, and Hessian computations as well as molecular properties such as atomic charges and vibrational frequency analysis. Both standard users and power users benefit from adopting these APIs as they lower the language barrier of input styles and enable a standard layout of variables and data. These designs allow end-to-end interoperable programming of complex computations and provide best practices options by default.

Rethinking Uncaging: A New Antiaromatic Photocage Driven by a Gain of Resonance Energy.

Photoactivatable compounds for example photoswitches or photolabile protecting groups (PPGs, photocages) for spatiotemporal light control, play a crucial role in different areas of research. For each application, parameters such as the absorption spectrum, solubility in the respective media and/or photochemical quantum yields for several competing processes need to be optimized. The design of new photochemical tools therefore remains an important task. In this study, we exploited the concept of excited-state-aromaticity, first described by N. Colin Baird in 1971, to investigate a new class of photocages, based on cyclic, ground-state-antiaromatic systems. Several thio- and nitrogen-functionalized compounds were synthesized, photochemically characterized and further optimized, supported by quantum chemical calculations. After choosing the optimal scaffold, which shows an excellent uncaging quantum yield of 28 %, we achieved a bathochromic shift of over 100 nm, resulting in a robust, well accessible, visible light absorbing, compact new photocage with a clean photoreaction and a high quantum product (ϵ⋅Φ) of 893 M-1 cm-1 at 405 nm.

Efficient Open-Source Implementations of Linear-Scaling Polarizable Embedding: Use Octrees to Save the Trees.

We present open-source implementations of the linear-scaling fast multipole method (FMM) within the polarizable embedding (PE) model for efficient treatment of large polarizable environments in computational spectroscopy simulations. The implementations are tested for accuracy, efficiency, and usability on model systems as well as more realistic biomolecular systems. We explain how FMM parameters affect the calculation of molecular properties and show that PE calculations employing FMM can be carried out in a black-box manner. The efficiency of the linear-scaling approach is demonstrated by simulating the UV/vis spectrum of a chromophore in an environment of more than 1 million polarizable sites. Our implementations are interfaced to several open-source quantum chemistry programs, making computational spectroscopy simulations within the PE model and FMM available to a large variety of methods and a broad user base.

Modeling Molecules under Pressure with Gaussian Potentials.

The computational modeling of molecules under high pressure is a growing research area that augments experimental high-pressure chemistry. Here, a new electronic structure method for modeling atoms and molecules under pressure, Gaussians On Surface Tesserae Simulate HYdrostatic Pressure (GOSTSHYP) approach, is introduced. In this method, a set of Gaussian potentials is distributed evenly on the van der Waals surface of the investigated chemical system, leading to a compression of the electron density and the atomic scaffold. Since no parameters other than pressure need to be specified, GOSTSHYP allows straightforward geometry optimizations and ab initio molecular dynamics simulations of chemical systems under pressure for nonexpert users. Calculated energies, bond lengths, and dipole moments under pressure fall within the range of established computational methods for high-pressure chemistry. A Diels-Alder reaction and the cyclotrimerization of acetylene showcase the ability of GOSTSHYP to model pressure-induced chemical reactions. The connection to mechanochemistry is pointed out.

Selective Modification for Red-Shifted Excitability: A Small Change in Structure, a Huge Change in Photochemistry.

We developed three bathochromic, green-light activatable, photolabile protecting groups based on a nitrodibenzofuran (NDBF) core with D-π-A push-pull structures. Variation of donor substituents (D) at the favored ring position enabled us to observe their impact on the photolysis quantum yields. Comparing our new azetidinyl-NDBF (Az-NDBF) photolabile protecting group with our earlier published DMA-NDBF, we obtained insight into its excitation-specific photochemistry. While the "two-photon-only" cage DMA-NDBF was inert against one-photon excitation (1PE) in the visible spectral range, we were able to efficiently release glutamic acid from azetidinyl-NDBF with irradiation at 420 and 530 nm. Thus, a minimal change (a cyclization adding only one carbon atom) resulted in a drastically changed photochemical behavior, which enables photolysis in the green part of the spectrum.

Complex excited state polarizabilities in the ADC/ISR framework.

We present the derivation and implementation of complex, frequency-dependent polarizabilities for excited states using the algebraic-diagrammatic construction for the polarization propagator (ADC) and its intermediate state representation. Based on the complex polarizability, we evaluate C6 dispersion coefficients for excited states. The methodology is implemented up to third order in perturbation theory in the Python-driven adcc toolkit for the development and application of ADC methods. We exemplify the approach using illustrative model systems and compare it to results from other ab initio methods and from experiments.

Recent developments in the PySCF program package.

PySCF is a Python-based general-purpose electronic structure platform that supports first-principles simulations of molecules and solids as well as accelerates the development of new methodology and complex computational workflows. This paper explains the design and philosophy behind PySCF that enables it to meet these twin objectives. With several case studies, we show how users can easily implement their own methods using PySCF as a development environment. We then summarize the capabilities of PySCF for molecular and solid-state simulations. Finally, we describe the growing ecosystem of projects that use PySCF across the domains of quantum chemistry, materials science, machine learning, and quantum information science.

Psi4 1.4: Open-source software for high-throughput quantum chemistry.

PSI4 is a free and open-source ab initio electronic structure program providing implementations of Hartree-Fock, density functional theory, many-body perturbation theory, configuration interaction, density cumulant theory, symmetry-adapted perturbation theory, and coupled-cluster theory. Most of the methods are quite efficient, thanks to density fitting and multi-core parallelism. The program is a hybrid of C++ and Python, and calculations may be run with very simple text files or using the Python API, facilitating post-processing and complex workflows; method developers also have access to most of PSI4's core functionalities via Python. Job specification may be passed using The Molecular Sciences Software Institute (MolSSI) QCSCHEMA data format, facilitating interoperability. A rewrite of our top-level computation driver, and concomitant adoption of the MolSSI QCARCHIVE INFRASTRUCTURE project, makes the latest version of PSI4 well suited to distributed computation of large numbers of independent tasks. The project has fostered the development of independent software components that may be reused in other quantum chemistry programs.

The rupture mechanism of rubredoxin is more complex than previously thought.

The surprisingly low rupture force and remarkable mechanical anisotropy of rubredoxin have been known for several years. Exploiting the first combination of steered molecular dynamics and the quantum chemical Judgement of Energy DIstribution (JEDI) analysis, the common belief that hydrogen bonds between neighboring amino acid backbones and the sulfur atoms of the central FeS4 unit in rubredoxin determine the low mechanical resistance of the protein is invalidated. The distribution of strain energy in the central part of rubredoxin is elucidated in real-time with unprecedented detail, giving important insights into the mechanical unfolding pathway of rubredoxin. While structural anisotropy as well as the contribution of angle bendings in the FeS4 unit have a significant influence on the mechanical properties of rubredoxin, these factors are insufficient to explain the experimentally observed low rupture force. Instead, the rupture mechanism of rubredoxin is far more complex than previously thought and requires more than just a hydrogen bond network.

CPPE: An Open-Source C++ and Python Library for Polarizable Embedding.

We present a modular open-source library for polarizable embedding (PE) named CPPE. The library is implemented in C++, and it additionally provides a Python interface for rapid prototyping and experimentation in a high-level scripting language. Our library integrates seamlessly with existing quantum chemical program packages through an intuitive and minimal interface. Until now, CPPE has been interfaced to three packages, Q-Chem, Psi4, and PySCF. Furthermore, we show CPPE in action using all three program packages for a computational spectroscopy application. With CPPE, host program interfaces only require minor programming effort, paving the way for new combined methodologies and broader availability of the PE model.

Polarizable Embedding Combined with the Algebraic Diagrammatic Construction: Tackling Excited States in Biomolecular Systems.

We present a variant of the algebraic diagrammatic construction (ADC) scheme by combining ADC with the polarizable embedding (PE) model. The presented PE-ADC method is implemented through second and third order and is designed with the aim of performing accurate calculations of excited states in large molecular systems. Accuracy and large-scale applicability are demonstrated with three case studies, and we further analyze the importance of both state-specific and linear-response-type corrections to the excitation energies in the presence of the polarizable environment. We demonstrate how our combined method can be readily applied to study photoinduced biochemical processes as we model the charge-transfer (CT) excitation which is key to the photoprotection mechanism in the dodecin protein with PE-ADC(2). Through direct access to state-of-the-art excited state analysis, we find that the polarizable environment plays a decisive role by significantly increasing the CT character of the electronic excitation in dodecin. PE-ADC is thus suited to decipher photoinduced processes in complex, biomolecular systems at high precision and at reasonable computational cost.

NAMD goes quantum: an integrative suite for hybrid simulations.

Hybrid methods that combine quantum mechanics (QM) and molecular mechanics (MM) can be applied to studies of reaction mechanisms in locations ranging from active sites of small enzymes to multiple sites in large bioenergetic complexes. By combining the widely used molecular dynamics and visualization programs NAMD and VMD with the quantum chemistry packages ORCA and MOPAC, we created an integrated, comprehensive, customizable, and easy-to-use suite (http://www.ks.uiuc.edu/Research/qmmm). Through the QwikMD interface, setup, execution, visualization, and analysis are streamlined for all levels of expertise.

PyContact: Rapid, Customizable, and Visual Analysis of Noncovalent Interactions in MD Simulations.

Molecular dynamics (MD) simulations have become ubiquitous in all areas of life sciences. The size and model complexity of MD simulations are rapidly growing along with increasing computing power and improved algorithms. This growth has led to the production of a large amount of simulation data that need to be filtered for relevant information to address specific biomedical and biochemical questions. One of the most relevant molecular properties that can be investigated by all-atom MD simulations is the time-dependent evolution of the complex noncovalent interaction networks governing such fundamental aspects as molecular recognition, binding strength, and mechanical and structural stability. Extracting, evaluating, and visualizing noncovalent interactions is a key task in the daily work of structural biologists. We have developed PyContact, an easy-to-use, highly flexible, and intuitive graphical user interface-based application, designed to provide a toolkit to investigate biomolecular interactions in MD trajectories. PyContact is designed to facilitate this task by enabling identification of relevant noncovalent interactions in a comprehensible manner. The implementation of PyContact as a standalone application enables rapid analysis and data visualization without any additional programming requirements, and also preserves full in-program customization and extension capabilities for advanced users. The statistical analysis representation is interactively combined with full mapping of the results on the molecular system through the synergistic connection between PyContact and VMD. We showcase the capabilities and scientific significance of PyContact by analyzing and visualizing in great detail the noncovalent interactions underlying the ion permeation pathway of the human P2X3 receptor. As a second application, we examine the protein-protein interaction network of the mechanically ultrastable cohesin-dockering complex.

Molecular Mechanism of Flavin Photoprotection by Archaeal Dodecin: Photoinduced Electron Transfer and Mg2+-Promoted Proton Transfer.

Photoinduced biochemical reactions are ubiquitously governed by derivatives of flavin, which is a key player in a manifold of cellular redox reactions. The photoreactivity of flavins is also one of their greatest disadvantages as the molecules are sensitive to photodegradation. To prevent this unfavorable reaction, UV-light-exposed archaea bacteria, such as Halobacterium salinarum, manage the task of protecting flavin derivatives by dodecin, a protein which stores flavins and efficiently photoprotects them. In this study, we shed light on the photoprotection mechanism, i.e., the excited state quenching mechanism by dodecin using computational methodology. Molecular dynamics (MD) simulations unraveled the hydrogen bond network in the flavin binding pocket as a starting point for proton transfer upon preceding electron transfer. Using high-level ab initio quantum chemical methods, different proton transfer channels have been investigated and an energetically feasible Mg2+-promoted channel has been identified fully explaining previous experimental observations. This is the first extensive theoretical study of archaeal dodecin, furthering the understanding of its photocycle and manipulation.