The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods Histone deacetylases (HDACs) are crucial enzymes involved in gene transcription and the regulation of various biological processes by removing acetyl groups from histones and other proteins. They play pivotal roles in diseases such as cancer, neurodegenerative disorders, and inflammatory conditions, making them potential therapeutic targets. This review discusses the structure and function of the four classes of human HDACs, highlighting the importance of computational methods in the discovery of HDAC inhibitors. These methods include ligand-based approaches, such as scaffold hopping, pharmacophore modeling, and structure-based virtual screening. Recent advancements in molecular dynamics simulations and Poisson–Boltzmann/molecular mechanics generalized Born surface area techniques have improved the prediction of ligand binding affinity. The review also explores the classification of HDACs into four subfamilies based on their structure, function, and sequence homology. The structural features of HDACs, including their catalytic domains and binding sites, are discussed, along with their roles in various biological processes. The review emphasizes the importance of understanding HDAC structure and function in the development of more effective and selective HDAC inhibitors. Additionally, the review highlights the impact of HDACs on diseases and the potential of computational-omics techniques in elucidating HDAC functionality and the inhibitory activity of HDAC inhibitors. The review also discusses the various HDAC inhibitors, their mechanisms of action, and their potential in cancer treatment. The review concludes with an overview of the current state of HDAC inhibitor research and the challenges in developing more effective and selective inhibitors.The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods Histone deacetylases (HDACs) are crucial enzymes involved in gene transcription and the regulation of various biological processes by removing acetyl groups from histones and other proteins. They play pivotal roles in diseases such as cancer, neurodegenerative disorders, and inflammatory conditions, making them potential therapeutic targets. This review discusses the structure and function of the four classes of human HDACs, highlighting the importance of computational methods in the discovery of HDAC inhibitors. These methods include ligand-based approaches, such as scaffold hopping, pharmacophore modeling, and structure-based virtual screening. Recent advancements in molecular dynamics simulations and Poisson–Boltzmann/molecular mechanics generalized Born surface area techniques have improved the prediction of ligand binding affinity. The review also explores the classification of HDACs into four subfamilies based on their structure, function, and sequence homology. The structural features of HDACs, including their catalytic domains and binding sites, are discussed, along with their roles in various biological processes. The review emphasizes the importance of understanding HDAC structure and function in the development of more effective and selective HDAC inhibitors. Additionally, the review highlights the impact of HDACs on diseases and the potential of computational-omics techniques in elucidating HDAC functionality and the inhibitory activity of HDAC inhibitors. The review also discusses the various HDAC inhibitors, their mechanisms of action, and their potential in cancer treatment. The review concludes with an overview of the current state of HDAC inhibitor research and the challenges in developing more effective and selective inhibitors.