用一致性模型加速分子骨架跳跃,生成速度提升30倍。
TurboHopp: Accelerated Molecule Scaffold Hopping with Consistency Models
- 结合骨架跳跃策略与一致性模型,实现快速生成。
- 推理速度比扩散模型快30倍,生成质量更优。
- 适合需要高效生成药物分子的科研与制药场景。
在药物发现中,探索可成药化合物的广阔化学空间是一项巨大挑战,生成模型正被越来越多地用于识别潜在候选物。基于三维结构的条件药物设计(3D-SBDD)模型因能考虑复杂的三维相互作用和分子几何结构而尤为有效。骨架跳跃是一种高效策略,通过有目的地修改分子核心结构,快速定位活性相似的化合物,从而缩小化学空间并提升类药分子的发现效率。然而,现有3D-SBDD生成模型的实际应用受限于其缓慢的处理速度。为此,我们提出TurboHopp,一种加速的口袋条件化3D骨架跳跃模型,融合传统骨架跳跃的战略性与一致性模型的快速生成能力。该协同机制不仅显著提升效率,还实现最高达30倍的推理速度提升,并在生成质量上优于现有扩散模型,确立了其在药物发现中的强大潜力。借助更快的推理速度,我们进一步引入基于强化学习的一致性模型(RLCM)优化,以生成理想分子。我们在多个药物发现场景中验证了TurboHopp的广泛适用性,凸显其在多样分子环境中的应用前景。
原文摘要 · Abstract (English)
Navigating the vast chemical space of druggable compounds is a formidable challenge in drug discovery, where generative models are increasingly employed to identify viable candidates. Conditional 3D structure-based drug design (3D-SBDD) models, which take into account complex three-dimensional interactions and molecular geometries, are particularly promising. Scaffold hopping is an efficient strategy that facilitates the identification of similar active compounds by strategically modifying the core structure of molecules, effectively narrowing the wide chemical space and enhancing the discovery of drug-like products. However, the practical application of 3D-SBDD generative models is hampered by their slow processing speeds. To address this bottleneck, we introduce TurboHopp, an accelerated pocket-conditioned 3D scaffold hopping model that merges the strategic effectiveness of traditional scaffold hopping with rapid generation capabilities of consistency models. This synergy not only enhances efficiency but also significantly boosts generation speeds, achieving up to 30 times faster inference speed as well as superior generation quality compared to existing diffusion-based models, establishing TurboHopp as a powerful tool in drug discovery. Supported by faster inference speed, we further optimize our model, using Reinforcement Learning for Consistency Models (RLCM), to output desirable molecules. We demonstrate the broad applicability of TurboHopp across multiple drug discovery scenarios, underscoring its potential in diverse molecular settings.
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