The eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) play a substantial role in Periodontal Disease (PD) due to their antimicrobial and immunomodulatory actions. However, their antimicrobial mechanism of action against bacteria involved in PD remains unclear. We aimed to estimate the probable targets of EPA and DHA against the seven periodontopathogens. Through in silico analyses, the protein-acids interactions, protein characterization, and molecular docking were performed. We identified 165 proteins from periodontopathogens that may interact with EPA and DHA. Fusobacterium nucleatum has the highest number of predicted proteins among analyzed bacteria (n = 43, 26.06%). The EPA shows more interactions than DHA. The EPA and DHA interact mainly with proteins involved in the metabolism (n = 69, 41.81%). Also, the EPA and DHA interact with proteins located in any subcellular location. The affinities between acids and pathogenic proteins were moderate (binding energy was lower than -4.0 kcal/mol). The interactions between EPA and DHA and periodontopathogens occur in multiples proteins. There is not a predilection about the functional class of pathogenic proteins targeting EPA and DHA. However, there are moderate binding affinities between EPA or DHA and essential pathogenic proteins (TolC, CRISPR, FusA).
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