论文标题
量子退火器上的多体分子对接
Multibody molecular docking on a quantum annealer
论文作者
论文摘要
分子对接旨在找到一组分子的最稳定的相互作用构型，对药物发现至关重要。尽管已经开发了大量的经典算法来进行分子对接，但大多数集中于对接两个分子的限制案例。由于N分子的可能构型的数量在N中是指数级的，因此允许对两个以上分子进行对接的例外尺寸较差，需要指数资源才能找到高质量的溶液。在这里，我们引入了多体分子对接问题的一列编码二次不受约束的二进制优化公式（QUBO），该公式适用于量子退火器的溶液。我们的方法涉及成对相互作用的经典预付，该预报仅在身体数量中二次缩放，同时允许使用Rosetta Ref2015 Energy函数（使用Rosetta Ref2015能量函数）。在第二步中，我们使用量子退火器有效地采样低能对接配置，并通过量子叠加同时考虑所有可能的对接配置。我们表明，我们能够通过调整用于执行单热编码的罚款的强度来最大程度地降低找到多样化的低能对接配置所需的时间，从而表明，通过常规的惩罚强度，解决方案质量和多样性在实现性能方面的多样性提高了3-4倍。 By mapping the configurational search to a form compatible with current- and future-generation quantum annealers, this work provides an alternative means of solving multibody docking problems that may prove to have performance advantages for large problems, potentially circumventing the exponential scaling of classical approaches and permitting a much more efficient solution to a problem central to drug discovery and validation pipelines.
Molecular docking, which aims to find the most stable interacting configuration of a set of molecules, is of critical importance to drug discovery. Although a considerable number of classical algorithms have been developed to carry out molecular docking, most focus on the limiting case of docking two molecules. Since the number of possible configurations of N molecules is exponential in N, those exceptions which permit docking of more than two molecules scale poorly, requiring exponential resources to find high-quality solutions. Here, we introduce a one-hot encoded quadratic unconstrained binary optimization formulation (QUBO) of the multibody molecular docking problem, which is suitable for solution by quantum annealer. Our approach involves a classical pre-computation of pairwise interactions, which scales only quadratically in the number of bodies while permitting well-vetted scoring functions like the Rosetta REF2015 energy function to be used. In a second step, we use the quantum annealer to sample low-energy docked configurations efficiently, considering all possible docked configurations simultaneously through quantum superposition. We show that we are able to minimize the time needed to find diverse low-energy docked configurations by tuning the strength of the penalty used to enforce the one-hot encoding, demonstrating a 3-4 fold improvement in solution quality and diversity over performance achieved with conventional penalty strengths. By mapping the configurational search to a form compatible with current- and future-generation quantum annealers, this work provides an alternative means of solving multibody docking problems that may prove to have performance advantages for large problems, potentially circumventing the exponential scaling of classical approaches and permitting a much more efficient solution to a problem central to drug discovery and validation pipelines.
