Fluorescent proteins are a class of important proteins for bio-imaging, protein interaction, expression monitoring and chemical detection. In particular, red fluorescent proteins have emission spectral that is less absorbed by the red blood cells when compared to green fluorescent proteins, thereby making them more useful as fluorescent makers in mammalian cells. Furthermore, the monomeric Red Fluorescent Protein is useful as a tag-fusion protein as it has fewer tendencies to form dimers and tetramers than other red fluorescent proteins. The fluorescent proteins differ in their utility due to their photo-toxicity, aggregation tendency and brightness. Residues on red fluorescent proteins were chosen for mutations using sequence alignment and computational methods involving the use of Boolean Learning Support Vector Machine (BLSVM) algorithm. Libraries of red fluorescent proteins were created using recombination and site-directed mutagenesis. The libraries were screened for improved functionality using spectrofluorometeric means. We will report protein engineering efforts on red fluorescent proteins, focusing on sequence-activity relationships of the red fluorescent proteins.