PlasmoSIP

Rationale:

Immunological responses against proteins from malaria parasites are dependent on a number of different factors. These include structural properties of proteins (i.e. protein 3D structure, protein disorder), interactions with the human immune system (MHC class I and class II presentation, recognition by B-cells) and antigen sequence polymorphism. To assist in the selection of novel vaccine candidates, markers of exposure, or potential biomarkers, we have developed PlasmoSIP. PlasmoSIP is an online resource which collates predictions for a number of structural and immunological parameters within Plasmodium species.

Protein sequences were obtained from PlasmoDB , and analysed using a number of computational prediction algorithms:

Prediction of protein disorder:

Intrinsically disordered proteins are unique in that they lack the typical secondary and tertiary structural elements that characterise many proteins. They are dynamic, highly flexible and have many important functional roles. Protein disorder was predicted using DISOPRED3 , which has been ranked as one of the best predictors of protein disorder by independent assessment (CASP10).

Prediction of MHC binding:

Presentation of pathogen-derived peptides via Major Histocompatibility Complex (MHC) molecules is crucial for development of both CD8+ and CD4+ T-cell responses (which recognise peptides presented in the context of MHC class I and MHC class II respectively). Prediction of MHC binding peptides was performed using NetMHC 3.0 (MHC class I) and NetMHCII (MHC class II), using all available MHC alleles.

Prediction of linear B-cell epitopes:

B-cell epitopes can be characterised as either linear or conformational. Linear B-cell epitopes are likely to be enriched within regions of protein disorder. Prediction of linear B-cell epitopes was performed using BepiPred.

Tandem repeats:

Protein tandem repeats have the potential to be immunodominant, as well as eliciting both T-independent and T-dependent B-cell responses. Identification of tandem repeats within Plasmodium proteins was performed using T-REKS.