标题： 基于通用可编程 RRAM 的概率计算机的首次硬件演示用于分子对接 显示英文标题

标题： The First Hardware Demonstration of a Universal Programmable RRAM-based Probabilistic Computer for Molecular Docking

摘要： 分子对接是药物设计和发现中的关键计算策略，但生物分子结构的复杂多样性和灵活的结合构象创造了巨大的搜索空间，这给传统计算方法带来了挑战。 尽管量子计算有望解决这些挑战，但它仍受到可扩展性、硬件限制和精度问题的制约。 在此，我们报告了一种概率计算机（p-计算机）的原型，该计算机首次高效且准确地解决了复杂的分子对接问题，克服了之前遇到的挑战。 系统的核心是一种基于我们人工可调概率位（p-位）的概率计算芯片，该芯片与基于180纳米CMOS技术和BEOL HfO2 RRAM的内存计算方案兼容。 我们在实际的配体-蛋白质对接场景中成功展示了p-计算机的优越性能。 成功解决了脂蛋白与LolA-LolCDE复合物的42节点分子对接问题——这是针对革兰氏阴性细菌开发抗生素的关键点。 我们的结果与蛋白质-配体相互作用分析工具高度一致。 这项工作标志着概率计算在基于分子对接的计算生物学中的首次应用，具有克服当前技术在解决复杂生物信息学问题时成功率和效率局限性的巨大潜力。 显示英文摘要

摘要： Molecular docking is a critical computational strategy in drug design and discovery, but the complex diversity of biomolecular structures and flexible binding conformations create an enormous search space that challenges conventional computing methods. Although quantum computing holds promise for these challenges, it remains constrained by scalability, hardware limitations, and precision issues. Here, we report a prototype of a probabilistic computer (p-computer) that efficiently and accurately solves complex molecular docking for the first time, overcoming previously encountered challenges. At the core of the system is a p-computing chip based upon our artificial tunable probabilistic bits (p-bits), which are compatible with computing-in-memory schemes, based upon 180 nm CMOS technology and BEOL HfO2 RRAM. We successfully demonstrated the superior performance of the p-computer in practical ligand-protein docking scenarios. A 42-node molecular docking problem of lipoprotein with LolA-LolCDE complex-a key point in developing antibiotics against Gram-negative bacteria, was successfully solved. Our results align well with the Protein-Ligand Interaction Profiler tool. This work marks the first application of p-computing in molecular docking-based computational biology, which has great potential to overcome the limitations in success rate and efficiency of current technologies in addressing complex bioinformatics problems.