Abstract

Rickettsia rickettsii is an aerobic, Gram-negative and non-motile coccobacillus known to cause Rocky Mountain spotted fever. The sequenced genome of its 'Sheila Smith' strain contains 1,343 protein-coding genes, 3 rRNA genes and 33 transfer RNA genes. There are 680 hypothetical proteins (HPs) present in the genome of R. rickettsii. Since functions of these proteins are not validated experimentally, characterization of these HPs may play a significant role in understanding the pathogenic mechanisms of R. rickettsii. Hence, functions of these HPs were annotated by in silico methods based on sequence similarity, protein clustering and protein-protein interactions. We have successfully predicted functions of 214 proteins among 680 HPs present in R. rickettsii. These annotated proteins were further classified into 88 enzymes, 59 transport and membrane proteins, 35 binding proteins, 12 structural motifs and the rest of the protein families. Moreover, we identified HPs involved in virulence among 214 functionally annotated proteins. 15 HPs were classified as virulence factors and two proteins with the highest scores were selected for further analyses. Additionally, molecular dynamics simulations were performed on these selected virulent HPs in order to observe their conformational behaviors. These analyses can further be utilized in the identification of new drug targets for development of better therapeutic agents against the infections caused by R. rickettsii.

Keywords: Rickettsia rickettsii, Molecular pathogenesis, Hypothetical proteins, Function prediction, Virulence, Molecular dynamics simulation.

Graphical Abstract