Measuring Interactions Between Proteins and Small Molecules or Nucleic Acids

Abstract Interactions between proteins and small molecules or nucleic acids play a pivotal role in numerous biological processes critical for human health and are fundamental for advancing our understanding of biological systems. Proteins are the workhorses of the cell, executing various functions ranging from catalyzing biochemical reactions to transmitting signals within the body. Small molecules, including drugs and metabolites, can modulate protein activity, thereby impacting cellular processes and disease pathways. Similarly, nucleic acids, such as DNA and RNA, regulate protein synthesis and function through intricate interactions. Understanding these interactions is crucial for drug discovery and development and can shed light on gene regulation, transcriptional control, and RNA processing, providing insights into genetic diseases and developmental disorders. Moreover, studying protein–small molecule and protein–nucleic acid interactions enhances our comprehension of fundamental biological mechanisms. A wide array of methods to study these interactions range in cost, sensitivity, materials usage, throughput, and complexity. Notably in the last decade, new techniques have been developed that enhance our understanding of these interactions. In this review, we aim to summarize the new state‐of‐the‐art methods for detecting interactions between proteins and small molecules or nucleic acids, as well as discuss older methods that still hold value today. © 2024 Wiley Periodicals LLC.