Modification with SUMO protein has many key roles in eukaryotic systems which renders the identification of its target proteins and sites of considerable importance. Information regarding the SUMOylation of a protein may tell us about its subcellular localization, function, and spatial orientation. This modification occurs at particular and not all lysine residues in a given protein. In competition with biochemical means of modified-site recognition, computational methods are strong contenders in the prediction of SUMOylation-undergoing sites on proteins. In this research, physicochemical properties of amino acids retrieved from AAIndex, especially those involved in docking of modifier and target proteins and optimal presentation of target lysine, in combination with sequence information and random forest-based classifier presented in WEKA have been used to develop a prediction model, SUMOhunt, with statistics significantly better than all previous predictors. In this model 97.56% accuracy, 100% sensitivity, 94% specificity, and 0.95 MCC have been achieved which shows that proposed amino acid properties have a significant role in SUMO attachment. SUMOhunt will hence bring great reliability and efficiency in SUMOylation prediction. 1. Introduction Posttranslational modifications on proteins offer spectacular diversity and functional variety to an organism’s otherwise constrained proteome. SUMOylation is one such PTM whose vast expanse of biological implications in organisms has brought it under attention; still till now many of its functional outcomes are not known. To name a few, SUMOylation is involved in transcriptional regulation [1–3], mRNA metabolism [4], apoptosis [5, 6], nuclear and subcellular transport [7, 8], protein trafficking [9], signal transduction [10], regulation of DNA damage and replication, cell-cycle progression, competition with other members of the ubiquitin family [2, 11, 12], prevention or promotion of deacetylation [13], chromosome segregation [14], structural integrity of chromatin and many proteins, and mitosis [15]. It has been reported to be involved in the perception of sound as well [16]. Also, it is known to participate in early developmental processes like cell differentiation, specification, division, and lineage commitment [17]. SUMOylation of a target protein can change its localization in a cell by altering its intermolecular and intramolecular interactions [18]. Hence, by determining whether a protein is SUMOylated or not, vital evidences can be gathered regarding its function and spatial association [19]. SUMO, a
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