MPRAP: An accessibility predictor for α-helical transmembrane proteins
(English)Manuscript (preprint) (Other academic)
Background: During the folding of a protein some residues will become exposed to the environmentwhile others will become buried in the protein interior. For water soluble proteins it is en-ergetically favorable to bury hydrophobic residues and expose polar and charged residues tothe surrounding water. However, transmembrane proteins face three distinct environments; ahydrophobic lipid environment inside the membrane, a hydrophilic water environment outsidethe membrane and a interface region rich in phospholipid head-groups. Therefore, for ener-getic reasons the accessible surfaces of transmembrane proteins need to expose different typesof residues at different locations. Results: In a set of structurally determined transmembrane proteins it was found that solvent ex-posed residues are quite different inside compared to outside the membrane. In contrast,residues buried within the interior of the protein are much more similar. Further, we foundthat state-of-the-art predictors for surface area are optimized for one of the environments andtherefore perform badly in the other environment. To circumvent this problem we developeda new predictor, MPRAP, that performs well both inside and outside the membrane regions aswell as being better than a combination of specialized predictors. A web-server of MPRAP isavailable at http://mprap.cbr.su.se/ Conclusion: By including complete α-helical transmembrane proteins in the training we developed apredictor that accurately predicts accessibility both inside and outside the membrane. This pre-dictor can aid in predicting 3D-structure, predicting functional relevance of individual residuesand identification of erroneous protein structures.
IdentifiersURN: urn:nbn:se:su:diva-35890OAI: oai:DiVA.org:su-35890DiVA: diva2:288598