|The high effectiveness of proteins in biological systems is a result of their mutational histories. A single amino acid substitution, the most frequent of changes in proteins, can alter their physiochemical properties and functions. Mutations impact protein folding and interactions, and thus their functions in a biological system. These mutations may be beneficial and identifying them can provide insights towards improving the engineering of proteins. Mutational analyses are extensively used to study protein structures and functions for different purposes. For therapeutic purposes, such analyses can lead to more efficient engineering of proteins: from identifying beneficial interactions for improving protein binding to identifying how point mutations in pathogens can impact immune responses in humans. Alternatively, the coronavirus pandemic has shown examples of how single point mutations in pathogens, like viruses, can lead to different variants with drastic consequences to human health; some variants may spread more easily in humans or show signs of resistance to existing treatment options. This has led to a belief that improved engineering of proteins towards therapeutic developments requires the study of protein interactions responsible for protein binding and functions. Both engineering native proteins and designing new proteins require computational techniques to overcome the perplexities of traditionally used experimental techniques. This dissertation is directed towards bridging the gap between computational protein structure and function by building a statistical understanding of various aspects of protein interactions and functions, thus contributing towards protein engineering techniques for therapeutic purposes. It is based on the hypothesis that knowledge about point mutations can then be directed towards developing an understanding of the structure to function relationship in proteins. Each chapter focuses on the effect of mutations on protein functions from a unique perspective. The chapters progress from characterizing the binding interfaces of therapeutic proteins to quantifying the effects of point mutations on protein binding, making an in-depth analysis of the effects of antigenic mutations on therapeutic protein interactions, and identifying the impact of viral mutations on immune responses in humans. The findings in each chapter can contribute to the study of engineering proteins to meet specific therapeutic needs.