D'Hondt Stijn, Oramas José, De Winter Hans
Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, IDLab, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
Department of Computer Science, Sint-Pietersvliet 7, 2000, Antwerp, Belgium.
J Cheminform. 2025 Apr 8;17(1):47. doi: 10.1186/s13321-025-00985-7.
It has become impossible to imagine the fields of biochemistry and medicinal chemistry without computational chemistry and molecular modelling techniques. In many steps of the drug development process in silico methods have become indispensable. Virtual screening (VS) can tremendously expedite the early discovery phase, whilst the use of molecular dynamics (MD) simulations forms a powerful additional tool to in vitro methods throughout the entire drug discovery process. In the field of biochemistry, MD has also become a compelling method for studying biophysical systems (e.g., protein folding) complementary to experimental techniques. However, both VS and MD come with their own limitations and methodological difficulties, from hardware limitations to restrictions in algorithmic capabilities. One solution to overcoming these difficulties lies in the field of machine learning (ML), and more specifically deep learning (DL). There are many ways in which DL can be applied to these molecular modelling techniques to achieve more accurate results in a more efficient manner or expedite the data analysis of the acquired results. Despite steadily increasing interest in DL amidst computational chemists, knowledge is still limited and scattered over different resources. This review is aimed at computational chemists with knowledge of molecular modelling, who wish to possibly integrate DL approaches in their research and already have a basic understanding of the fundamentals of DL. This review focusses on a survey of recent applications of DL in molecular modelling techniques. The different sections are logically subdivided, based on where DL is integrated in the research: (1) for the improvement of VS workflows, (2) for the improvement of certain workflows in MD simulations, (3) for aiding in the calculations of interatomic forces, or (4) for data analysis of MD trajectories. It will become clear that DL has the capacity to completely transform the way molecular modelling is carried out.
很难想象没有计算化学和分子建模技术,生物化学和药物化学领域会是什么样子。在药物开发过程的许多步骤中,计算机模拟方法已变得不可或缺。虚拟筛选(VS)可以极大地加快早期发现阶段,而分子动力学(MD)模拟的使用则在整个药物发现过程中形成了一种强大的辅助体外方法的工具。在生物化学领域,MD也已成为一种用于研究生物物理系统(例如蛋白质折叠)的引人注目的方法,可作为实验技术的补充。然而,VS和MD都有其自身的局限性和方法上的困难,从硬件限制到算法能力的限制。克服这些困难的一种解决方案在于机器学习(ML)领域,更具体地说是深度学习(DL)。DL可以通过多种方式应用于这些分子建模技术,以更高效的方式获得更准确的结果或加快对所得结果的数据分析。尽管计算化学家对DL的兴趣在稳步增加,但相关知识仍然有限且分散在不同的资源中。这篇综述针对的是具有分子建模知识的计算化学家,他们希望在研究中可能整合DL方法,并且已经对DL的基本原理有基本的了解。这篇综述重点介绍了DL在分子建模技术中的最新应用。根据DL在研究中的整合位置,不同的部分进行了合理细分:(1)用于改进VS工作流程,(2)用于改进MD模拟中的某些工作流程,(3)用于辅助计算原子间力,或(4)用于MD轨迹的数据分析。很明显,DL有能力彻底改变分子建模的方式。