Multi-objective Bayesian optimization (MOBO) provides a principled framework for navigating trade-offs in molecular design. However, its empirical advantages over scalarized alternatives remain underexplored. We benchmark a simple Pareto-based MOBO strategy - Expected Hypervolume Improvement (EHVI) - against a simple fixed-weight scalarized baseline using Expected Improvement (EI), under a tightly controlled setup with identical Gaussian Process surrogates and molecular representations. Across three molecular optimization tasks, EHVI consistently outperforms scalarized EI in terms of Pareto front coverage, convergence speed, and chemical diversity. While scalarization encompasses flexible variants - including random or adaptive schemes - our results show that even strong deterministic instantiations can underperform in low-data regimes. These findings offer concrete evidence for the practical advantages of Pareto-aware acquisition in de novo molecular optimization, especially when evaluation budgets are limited and trade-offs are nontrivial.
翻译:多目标贝叶斯优化(MOBO)为分子设计中的权衡探索提供了理论框架,但其相较于标量化方法的实际优势尚未得到充分验证。本研究在严格控制的实验设置下(采用相同的高斯过程代理模型与分子表征),将基于帕累托前沿的简单MOBO策略——期望超体积改进(EHVI)与使用期望改进(EI)的固定权重标量化基线进行系统对比。在三个分子优化任务中,EHVI在帕累托前沿覆盖率、收敛速度和化学多样性方面均持续优于标量化EI。尽管标量化方法包含随机或自适应机制等灵活变体,但实验结果表明,即使在强确定性设定下,其在低数据区域仍可能表现欠佳。这些发现为帕累托感知采集函数在从头分子优化中的实际优势提供了具体证据,特别当评估预算有限且目标间存在显著权衡时。