Determination of three dimensional structure of scaA protein, a virulence factor of Streptococcus gordonii by homology modelling and design of inhibitors for scaA protein

Streptococcus gordonii are one among the early colonisers of tooth surfaces of humans and are present in coronal plaque, gingival crevices and buccal and pharyngeal mucosal surfaces. One of the main virulence factor that is involved in S. gordonii adhesion and coaggregation is ScaA protein. Inactivation of scaA genes resulted in both impaired growth of cells and inhibition of Mn2+ intake. Thus the inhibitors of ScaA protein can act as an effective drug against S. gordonii especially in the prevention and treatment of infective endocarditis and dental caries. The three dimensional structure of ScaA protein is predicted by homology modelling. It is the method to determine 3D structure of protein with the help of 3D structure of homologous proteins. Softwares used are Modeller 9.11 and Easy modeller 2.0 GUI. A total of 500 ligands in 2D format were derived from myricetin with the help of software ACD chemsketch. Rapid virtual screenings of these compounds were performed in the docking tool iGEMDOCK v2.0. Based on the binding energy a total of three ligands were selected for the further study. Three ligands thus generated possessed very good docking energy. Thus three ligands with good inhibitory properties were generated among which 5-[3,4-dihydroxy-6-(pyridin-2-yl)-8aH-chromen-2-yl]benzene-1,2,3-triol, a novel compound is found to be very excellent drug candidate based on the molecular docking studies and its ADME properties.