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Synaptic vesicle transport by motor proteins along microtubules is a crucially active process underlying neuronal communication. It is known that microtubules are destabilized by tau-hyperphosphorylation, which causes tau proteins to detach from microtubules and form neurofibril tangles. However, how tau-phosphorylation affects the transport dynamics of motor proteins on the microtubule remains unknown. Here, we discover that the long-distance unidirectional motion of vesicle-motor protein multiplexes (VMPMs) in living cells is suppressed under tau-hyperphosphorylation, with the consequent loss of fast vesicle-transport along the microtubule. The VMPMs in hyperphosphorylated cells exhibit seemingly bidirectional random motion, with dynamic properties far different from those of VMPM motion in normal cells. We establish a parsimonious physicochemical model of VMPM’s active motion that provides a unified, quantitative explanation and predictions for our experimental results. Our analysis reveals that, under hyperphosphorylation conditions, motor protein multiplexes have both static and dynamic motility fluctuations. The loss of fast vesicle-transport along the microtubule can be a mechanism of neurodegenerative disorders associated with tau-hyperphosphorylation.

The electron pair approximation offers an efficient variational quantum eigensolver (VQE) approach for chemistry simulations on quantum computers. With the number of entangling gates scaling quadratically with system size and a constant measurement overhead, the orbital optimized unitary pair coupled cluster double (oo-upCCD) ansatz strikes a balance between accuracy and efficiency. However, the electron pair approximation prevents the method from achieving quantitative accuracy. To improve it, we explore the theory of second order perturbation (PT2) correction to oo-upCCD. PT2 accounts for the missing broken-pair contributions in oo-upCCD, while retaining its efficiencies. For molecular bond stretching and chemical reactions, the method significantly improves the predicted energy accuracy, reducing oo-upCCD's error by up to 90%. On IonQ's quantum computers, we find that the PT2 energy correction is highly noise-resilient. The predicted VQE-PT2 reaction energies are in excellent agreement with noise-free simulators after applying simple error mitigations solely on the VQE energies. [ABSTRACT FROM AUTHOR]

The realization of quantum advantage with noisy-intermediate-scale quantum (NISQ) machines has become one of the major challenges in computational sciences. Maintaining coherence of a physical system with more than ten qubits is a critical challenge that motivates research on compact system representations to reduce algorithm complexity. Toward this end, the variational quantum eigensolver (VQE) used to perform quantum simulations is considered to be one of the most promising algorithms for quantum chemistry in the NISQ era. We investigate reduced mapping of one spatial orbital to a single qubit to analyze the ground state energy in a way that the Pauli operators of qubits are mapped to the creation/annihilation of singlet pairs of electrons. To include the effect of non-bosonic (or non-paired) excitations, we introduce a simple correction scheme in the electron correlation model approximated by the geometrical mean of the bosonic (or paired) terms. Employing it in a VQE algorithm, we assess ground state energies of H2O, N2, and Li2O in good agreement with full configuration interaction (FCI) models respectively, using only 6, 8, and 12 qubits with quantum gate depths proportional to the squares of the qubit counts. With the adopted seniority-zero approximation that uses only one half of the qubit counts of a conventional VQE algorithm, we find that our non-bosonic correction method reaches reliable quantum chemistry simulations at least for the tested systems. [ABSTRACT FROM AUTHOR]