Prioritizing quantum computing use cases in the drug discovery and development pipeline.

Recent innovations in quantum computing hardware and algorithms have raised expectations that practical, real-world applications are within reach. In this context, we explore the potential impact of quantum computing on the drug discovery and development pipeline. Specifically, we discuss use cases from our research programs and outline approaches for prioritizing them based on our assessment of potential benefit from quantum computation.

A general framework for active space embedding methods with applications in quantum computing.

We developed a general framework for hybrid quantum-classical computing of molecular and periodic embedding approaches based on an orbital space separation of the fragment and environment degrees of freedom. We demonstrate its potential by presenting a specific implementation of periodic range-separated DFT coupled to a quantum circuit ansatz, whereby the variational quantum eigensolver and the quantum equation-of-motion algorithm are used to obtain the low-lying spectrum of the embedded fragment Hamiltonian. The application of this scheme to study localized electronic states in materials is showcased through the accurate prediction of the optical properties of the neutral oxygen vacancy in magnesium oxide (MgO).

Hardware-tailored diagonalization circuits.

A central building block of many quantum algorithms is the diagonalization of Pauli operators. Although it is always possible to construct a quantum circuit that simultaneously diagonalizes a given set of commuting Pauli operators, only resource-efficient circuits can be executed reliably on near-term quantum computers. Generic diagonalization circuits, in contrast, often lead to an unaffordable SWAP gate overhead on quantum devices with limited hardware connectivity.

Nonadiabatic Molecular Dynamics with Fermionic Subspace-Expansion Algorithms on Quantum Computers.

We introduce a novel computational framework for excited-state molecular quantum dynamics simulations driven by quantum-computing-based electronic-structure calculations. This framework leverages the fewest-switches surface-hopping method for simulating the nuclear dynamics and calculates the required excited-state transition properties with different flavors of the quantum subspace expansion and quantum equation-of-motion algorithms. We apply our method to simulate the collision reaction between a hydrogen atom and a hydrogen molecule.

Ultrafast fragmentation of highly-excited doubly-ionized deoxyribose: role of the liquid water environment.

molecular dynamics simulations are used to investigate the fragmentation dynamics following the double ionization of 2-deoxy-D-ribose (DR), a major component in the DNA chain. Different ionization scenarios are considered to provide a complete picture. First focusing on isolated DR, fragmentation patterns are determined for the ground electronic state, adding randomly distributed excitation energy to the nuclei.

The odd-number cyclo[13]carbon and its dimer, cyclo[26]carbon.

Molecular rings of carbon atoms (cyclo[]carbons, or C) are excellent benchmarking systems for testing quantum chemical theoretical methods and valuable precursors to other carbon-rich materials. Odd- cyclocarbons, which have been elusive to date, are predicted to be even less stable than even- cyclocarbons. We report the on-surface synthesis of cyclo[13]carbon, C, by manipulation of decachlorofluorene with a scanning probe microscope tip.

Quantum algorithms for quantum dynamics.

Among the many computational challenges faced across different disciplines, quantum-mechanical systems pose some of the hardest ones and offer a natural playground for the growing field of quantum technologies. In this Perspective, we discuss quantum algorithmic solutions for quantum dynamics, reporting on the latest developments and offering a viewpoint on their potential and current limitations. We present some of the most promising areas of application and identify possible research directions for the coming years.

Toward Accurate Post-Born-Oppenheimer Molecular Simulations on Quantum Computers: An Adaptive Variational Eigensolver with Nuclear-Electronic Frozen Natural Orbitals.

Nuclear quantum effects such as zero-point energy and hydrogen tunneling play a central role in many biological and chemical processes. The nuclear-electronic orbital (NEO) approach captures these effects by treating selected nuclei quantum mechanically on the same footing as electrons. On classical computers, the resources required for an exact solution of NEO-based models grow exponentially with system size.

Aromaticity Reversal Induced by Vibrations in Cyclo[16]carbon.

Aromaticity is typically regarded as an intrinsic property of a molecule, correlated with electron delocalization, stability, and other properties. Small variations in the molecular geometry usually result in small changes in aromaticity, in line with Hammond's postulate. For example, introducing bond-length alternation in benzene and square cyclobutadiene by modulating the geometry along the Kekulé vibration gradually decreases the magnitude of their ring currents, making them less aromatic and less antiaromatic, respectively.

On-surface synthesis of a doubly anti-aromatic carbon allotrope.

Synthetic carbon allotropes such as graphene, carbon nanotubes and fullerenes have revolutionized materials science and led to new technologies. Many hypothetical carbon allotropes have been discussed, but few have been studied experimentally. Recently, unconventional synthetic strategies such as dynamic covalent chemistry and on-surface synthesis have been used to create new forms of carbon, including γ-graphyne, fullerene polymers, biphenylene networks and cyclocarbons.

Spin-Flip Unitary Coupled Cluster Method: Toward Accurate Description of Strong Electron Correlation on Quantum Computers.

Quantum computers have emerged as a promising platform to simulate strong electron correlation that is crucial to catalysis and photochemistry. However, owing to the choice of a trial wave function employed in the variational quantum eigensolver (VQE) algorithm, accurate simulation is restricted to certain classes of correlated phenomena. Herein, we combine the spin-flip (SF) formalism with the unitary coupled cluster with singles and doubles (UCCSD) method via the quantum equation-of-motion (qEOM) approach to allow for an efficient simulation of a large family of strongly correlated problems.

Nonadiabatic Nuclear-Electron Dynamics: A Quantum Computing Approach.

Coupled quantum electron-nuclear dynamics is often associated with the Born-Huang expansion of the molecular wave function and the appearance of nonadiabatic effects as a perturbation. On the other hand, native multicomponent representations of electrons and nuclei also exist, which do not rely on any a priori approximation. However, their implementation is hampered by prohibitive scaling.

Optimizing Quantum Classification Algorithms on Classical Benchmark Datasets.

The discovery of quantum algorithms offering provable advantages over the best known classical alternatives, together with the parallel ongoing revolution brought about by classical artificial intelligence, motivates a search for applications of quantum information processing methods to machine learning. Among several proposals in this domain, quantum kernel methods have emerged as particularly promising candidates. However, while some rigorous speedups on certain highly specific problems have been formally proven, only empirical proof-of-principle results have been reported so far for real-world datasets.

A quantum computing implementation of nuclearelectronic orbital (NEO) theory: Toward an exact pre-Born-Oppenheimer formulation of molecular quantum systems.

Nuclear quantum phenomena beyond the Born-Oppenheimer approximation are known to play an important role in a growing number of chemical and biological processes. While there exists no unique consensus on a rigorous and efficient implementation of coupled electron-nuclear quantum dynamics, it is recognized that these problems scale exponentially with system size on classical processors and, therefore, may benefit from quantum computing implementations. Here, we introduce a methodology for the efficient quantum treatment of the electron-nuclear problem on near-term quantum computers, based upon the Nuclear-Electronic Orbital (NEO) approach.

Quantum Embedding Method for the Simulation of Strongly Correlated Systems on Quantum Computers.

Quantum computing has emerged as a promising platform for simulating strongly correlated systems in chemistry, for which the standard quantum chemistry methods are either qualitatively inaccurate or too expensive. However, due to the hardware limitations of the available noisy near-term quantum devices, their application is currently limited only to small chemical systems. One way for extending the range of applicability can be achieved within the quantum embedding approach.

Selectivity in single-molecule reactions by tip-induced redox chemistry.

Controlling selectivity of reactions is an ongoing quest in chemistry. In this work, we demonstrate reversible and selective bond formation and dissociation promoted by tip-induced reduction-oxidation reactions on a surface. Molecular rearrangements leading to different constitutional isomers are selected by the polarity and magnitude of applied voltage pulses from the tip of a combined scanning tunneling and atomic force microscope.

Molecular Quantum Dynamics: A Quantum Computing Perspective.

ConspectusSimulating molecular dynamics (MD) within a comprehensive quantum framework has been a long-standing challenge in computational chemistry. An exponential scaling of computational cost renders solving the time dependent Schrödinger equation (TDSE) of a molecular Hamiltonian, including both electronic and nuclear degrees of freedom (DOFs), as well as their couplings, infeasible for more than a few DOFs. In the Born-Oppenheimer (BO), or adiabatic, picture, electronic and nuclear parts of the wave function are decoupled and treated separately.

Assessing the Nature of Chiral-Induced Spin Selectivity by Magnetic Resonance.

Understanding chiral-induced spin selectivity (CISS), resulting from charge transport through helical systems, has recently inspired many experimental and theoretical efforts but is still the object of intense debate. In order to assess the nature of CISS, we propose to focus on electron-transfer processes occurring at the single-molecule level. We design simple magnetic resonance experiments, exploiting a qubit as a highly sensitive and coherent magnetic sensor, to provide clear signatures of the acceptor polarization.

Quantum algorithm for alchemical optimization in material design.

The development of tailored materials for specific applications is an active field of research in chemistry, material science and drug discovery. The number of possible molecules obtainable from a set of atomic species grow exponentially with the size of the system, limiting the efficiency of classical sampling algorithms. On the other hand, quantum computers can provide an efficient solution to the sampling of the chemical compound space for the optimization of a given molecular property.

Improved Accuracy on Noisy Devices by Nonunitary Variational Quantum Eigensolver for Chemistry Applications.

We propose a modification of the Variational Quantum Eigensolver algorithm for electronic structure optimization using quantum computers, named nonunitary Variational Quantum Eigensolver (nu-VQE), in which a nonunitary operator is combined with the original system Hamiltonian leading to a new variational problem with a simplified wave function ansatz. In the present work, as nonunitary operator, we use the Jastrow factor, inspired from classical Quantum Monte Carlo techniques for simulation of strongly correlated electrons. The method is applied to prototypical molecular Hamiltonians for which we obtain accurate ground-state energies with shallower circuits, at the cost of an increased number of measurements.

Probing Molecular Excited States by Atomic Force Microscopy.

By employing single charge injections with an atomic force microscope, we investigated redox reactions of a molecule on a multilayer insulating film. First, we charged the molecule positively by attaching a single hole. Then we neutralized it by attaching an electron and observed three channels for the neutralization.

Quantum HF/DFT-embedding algorithms for electronic structure calculations: Scaling up to complex molecular systems.

In the near future, material and drug design may be aided by quantum computer assisted simulations. These have the potential to target chemical systems intractable by the most powerful classical computers. However, the resources offered by contemporary quantum computers are still limited, restricting the simulations to very simple molecules.

Nonadiabatic Molecular Quantum Dynamics with Quantum Computers.

The theoretical investigation of nonadiabatic processes is hampered by the complexity of the coupled electron-nuclear dynamics beyond the Born-Oppenheimer approximation. Classically, the simulation of such reactions is limited by the unfavorable scaling of the computational resources as a function of the system size. While quantum computing exhibits proven quantum advantage for the simulation of real-time dynamics, the study of quantum algorithms for the description of nonadiabatic phenomena is still unexplored.

Quantum equilibration of the double-proton transfer in a model system porphine.

There is a renewed interest in the derivation of statistical mechanics from the dynamics of closed quantum systems. A central part of this program is to understand how closed quantum systems, i.e.