Mathematical Optimization in Machine Learning for Computational Chemistry

Machine learning (ML) is transforming computational chemistry by accelerating molecular simulations, property prediction, and inverse design. Central to this transformation is mathematical optimization, which underpins nearly every stage of model development, from training neural networks and tuning...

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Main Author: Ana Zekić
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Computation
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Online Access:https://www.mdpi.com/2079-3197/13/7/169
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author Ana Zekić
author_facet Ana Zekić
author_sort Ana Zekić
collection DOAJ
description Machine learning (ML) is transforming computational chemistry by accelerating molecular simulations, property prediction, and inverse design. Central to this transformation is mathematical optimization, which underpins nearly every stage of model development, from training neural networks and tuning hyperparameters to navigating chemical space for molecular discovery. This review presents a structured overview of optimization techniques used in ML for computational chemistry, including gradient-based methods (e.g., SGD and Adam), probabilistic approaches (e.g., Monte Carlo sampling and Bayesian optimization), and spectral methods. We classify optimization targets into model parameter optimization, hyperparameter selection, and molecular optimization and analyze their application across supervised, unsupervised, and reinforcement learning frameworks. Additionally, we examine key challenges such as data scarcity, limited generalization, and computational cost, outlining how mathematical strategies like active learning, meta-learning, and hybrid physics-informed models can address these issues. By bridging optimization methodology with domain-specific challenges, this review highlights how tailored optimization strategies enhance the accuracy, efficiency, and scalability of ML models in computational chemistry.
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spelling doaj-art-0dc44aef6bf543dc9d98f61c137a0e472025-08-20T03:08:00ZengMDPI AGComputation2079-31972025-07-0113716910.3390/computation13070169Mathematical Optimization in Machine Learning for Computational ChemistryAna Zekić0Department of Mathematical Sciences, Faculty of Technology and Metallurgy, University of Belgrade, 11000 Belgrade, SerbiaMachine learning (ML) is transforming computational chemistry by accelerating molecular simulations, property prediction, and inverse design. Central to this transformation is mathematical optimization, which underpins nearly every stage of model development, from training neural networks and tuning hyperparameters to navigating chemical space for molecular discovery. This review presents a structured overview of optimization techniques used in ML for computational chemistry, including gradient-based methods (e.g., SGD and Adam), probabilistic approaches (e.g., Monte Carlo sampling and Bayesian optimization), and spectral methods. We classify optimization targets into model parameter optimization, hyperparameter selection, and molecular optimization and analyze their application across supervised, unsupervised, and reinforcement learning frameworks. Additionally, we examine key challenges such as data scarcity, limited generalization, and computational cost, outlining how mathematical strategies like active learning, meta-learning, and hybrid physics-informed models can address these issues. By bridging optimization methodology with domain-specific challenges, this review highlights how tailored optimization strategies enhance the accuracy, efficiency, and scalability of ML models in computational chemistry.https://www.mdpi.com/2079-3197/13/7/169mathematical optimizationmachine learning in chemistrycomputational chemistryBayesian optimization
spellingShingle Ana Zekić
Mathematical Optimization in Machine Learning for Computational Chemistry
Computation
mathematical optimization
machine learning in chemistry
computational chemistry
Bayesian optimization
title Mathematical Optimization in Machine Learning for Computational Chemistry
title_full Mathematical Optimization in Machine Learning for Computational Chemistry
title_fullStr Mathematical Optimization in Machine Learning for Computational Chemistry
title_full_unstemmed Mathematical Optimization in Machine Learning for Computational Chemistry
title_short Mathematical Optimization in Machine Learning for Computational Chemistry
title_sort mathematical optimization in machine learning for computational chemistry
topic mathematical optimization
machine learning in chemistry
computational chemistry
Bayesian optimization
url https://www.mdpi.com/2079-3197/13/7/169
work_keys_str_mv AT anazekic mathematicaloptimizationinmachinelearningforcomputationalchemistry