Modularization of multi-qubit controlled phase gate and its NMR implementation

Quantum circuit network is a set of circuits that implements a certain computation task. Being at the center of the quantum circuit network, the multi-qubit controlled phase shift is one of the most important quantum gates. In this paper, we apply the method of modular structuring in classical computer architecture to quantum computer and give a recursive realization of the multi-qubit phase gate. This realization of the controlled phase shift gate is convenient in realizing certain quantum algorithms. We have experimentally implemented this modularized multi-qubit controlled phase gate in a three qubit nuclear magnetic resonance quantum system. The network is demonstrated experimentally using line selective pulses in nuclear magnetic resonance technique. The procedure has the advantage of being simple and easy to implement.Comment: to appear in Journal of Optics B: Quantum and Semiclassical Optic

Structural basis of PROTAC cooperative recognition for selective protein degradation

Inducing macromolecular interactions with small molecules to activate cellular signaling is a challenging goal. PROTACs (proteolysis-targeting chimeras) are bifunctional molecules that recruit a target protein in proximity to an E3 ubiquitin ligase to trigger protein degradation. Structural elucidation of the key ternary ligase-PROTAC-target species and its impact on target degradation selectivity remain elusive. We solved the crystal structure of Brd4 degrader MZ1 in complex with human VHL and the Brd4 bromodomain (Brd4BD2). The ligand folds into itself to allow formation of specific intermolecular interactions in the ternary complex. Isothermal titration calorimetry studies, supported by surface mutagenesis and proximity assays, are consistent with pronounced cooperative formation of ternary complexes with Brd4BD2. Structure-based-designed compound AT1 exhibits highly selective depletion of Brd4 in cells. Our results elucidate how PROTAC-induced de novo contacts dictate preferential recruitment of a target protein into a stable and cooperative complex with an E3 ligase for selective degradation