Interpretable Meta-Learning for Multi-Objective Chemical Search

2026-06-18

AI Summary

This work addresses the challenge of balancing efficiency, interpretability, and performance in multi-objective molecular search under limited computational resources. The authors propose a novel approach that integrates interpretable linear meta-learning with adaptive confidence-based uncertainty quantification within an Efficient Global Optimization (EGO) framework. This is the first study to incorporate linear meta-learning into multi-objective chemical space exploration, complemented by a dynamic confidence-tuning algorithm that adaptively balances exploration and exploitation. Evaluated on large-scale searches for spin-crossover metal–organic complexes, the method achieves a 78% performance improvement over baseline approaches, with the dynamic tuning strategy significantly outperforming static calibration at the 50% confidence level.

Abstract

Navigating the vast space of synthetically accessible molecules demands surrogate models that are interpretable and capable of handling multiple competing objectives at the same time. Deep learning approaches struggle to satisfy them under the computational constraints of quantum-level chemistry. Here, we introduce a modular pipeline that combines interpretable linear meta-learning models and adaptive-confidence uncertainty quantification into an Efficient Global Optimization (EGO) framework for multi-objective molecular discovery. For the first time, linear meta-learning is deployed in a multi-objective chemical search setting: by training across chemical objectives and cheap auxiliary properties, the meta-learned surrogates acquire transferable chemical knowledge that adapts rapidly to new objectives from limited data. Evaluated empirically on a real large scale search for spin-crossover metal-organic complexes, the baseline performs 78% worse in Pareto sense than the meta-learning alternative. We also address the calibration challenges inherent to active search. Since optimal candidates typically lie precisely in the distributional tails, standard uncertainty estimates fail. We introduce an adaptive confidence-tuning algorithm that dynamically recalibrates the exploration-exploitation trade-off as the molecular search evolves. Empirically, dynamic confidence tuning further dominates over 50% of the statically calibrated front.

Problem

• multi-objective chemical search
• interpretable surrogate models
• uncertainty quantification
• active learning
• molecular discovery

Innovation

• interpretable meta-learning
• multi-objective molecular discovery
• adaptive confidence tuning
• efficient global optimization
• uncertainty quantification