Electronegativity and intrinsic disorder of preeclampsia-related proteins

Preeclampsia, hemorrhage, and infection are the leading causes of maternal death in underdeveloped countries. Since several proteins associated with preeclampsia are known, we conducted a computational study which evaluated the commonness and potential functionality of intrinsic disorder of these proteins and also made an attempt to characterize their origin. The origin of the preeclampsia-related proteins was assessed with a supervised technique, a Polarity Index Method (PIM), which evaluates the electronegativity of proteins based solely on their sequence. The commonness of intrinsic disorder was evaluated using several disorder predictors from the PONDR family, the charge-hydropathy plot (CH-plot) and cumulative distribution function (CDF) analyses, and using the MobiDB web-based tool, whereas potential functionality of intrinsic disorder was studied with the D2P2 resource and ANCHOR predictor of disorder-based binding sites, and the STRING tool was used to build the interactivity networks of the preeclampsia-related proteins. Peculiarities of the PIM-derived polar profile of the group of preeclampsia-related proteins were then compared with profiles of a group of lipoproteins, antimicrobial peptides, angiogenesis-related proteins, and the intrinsically disordered proteins. Our results showed a high graphical correlation between preeclampsia proteins, lipoproteins, and the angiogenesis proteins. We also showed that many preeclampsia-related proteins contain numerous functional disordered regions. Therefore, these bioinformatics results led us to assume that the preeclampsia proteins are highly associated with the lipoproteins group, and that some preeclampsia-related proteins contain significant amounts of functional disorders.