A comprehensive review of computational methods for Protein-DNA binding site prediction.
Journal:
Analytical biochemistry
Published Date:
Apr 8, 2025
Abstract
Accurately identifying protein-DNA binding sites is essential for understanding the molecular mechanisms underlying biological processes, which in turn facilitates advancements in drug discovery and design. While biochemical experiments provide the most accurate way to locate DNA-binding sites, they are generally time-consuming, resource-intensive, and expensive. There is a pressing need to develop computational methods that are both efficient and accurate for DNA-binding site prediction. This study thoroughly reviews and categorizes major computational approaches for predicting DNA-binding sites, including template detection, statistical machine learning, and deep learning-based methods. The 14 state-of-the-art DNA-binding site prediction models have been benchmarked on 136 non-redundant proteins, where the deep learning-based, especially pre-trained large language model-based, methods achieve superior performance over the other two categories. Applications of these DNA-binding site prediction methods are also involved.