title: Statistical prediction of protein structural, localization and functional properties by the analysis of its fragment mass distributions after proteolytic cleavage.
abstract: Structural, localization and functional properties of unknown proteins are often being predicted from their primary polypeptide chains using sequence alignment with already characterized proteins and consequent molecular modeling. Here we suggest an approach to predict various structural and structure-associated properties of proteins directly from the mass distributions of their proteolytic cleavage fragments. For amino-acid-specific cleavages, the distributions of fragment masses are determined by the distributions of inter-amino-acid intervals in the protein, that in turn apparently reflect its structural and structure-related features. Large-scale computer simulations revealed that for transmembrane proteins, either α-helical or β -barrel secondary structure could be predicted with about 90% accuracy after thermolysin cleavage. Moreover, 3/4 intrinsically disordered proteins could be correctly distinguished from proteins with fixed three-dimensional structure belonging to all four SCOP structural classes by combining 3-4 different cleavages. Additionally, in some cases the protein cellular localization (cytosolic or membrane-associated) and its host organism (Firmicute or Proteobacteria) could be predicted with around 80% accuracy. In contrast to cytosolic proteins, for membrane-associated proteins exhibiting specific structural conformations, their monotopic or transmembrane localization and functional group (ATP-binding, transporters, sensors and so on) could be also predicted with high accuracy and particular robustness against missing cleavages.
authors.affiliation: Biomedical Engineering Research Center, St. Petersburg Electrotechnical University, St. Petersburg, 197376, Russia.
authors.forename: Mikhail I
authors.initials: MI
authors.lastname: Bogachev
authors.affiliation: Department of Genetics, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Tatarstan, 420008, Russia.
authors.forename: Airat R
authors.initials: AR
authors.lastname: Kayumov
authors.affiliation: Biomedical Engineering Research Center, St. Petersburg Electrotechnical University, St. Petersburg, 197376, Russia.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Markelov
authors.affiliation: Institut für Theoretische Physik, Justus-Liebig-Universität Giessen, 35392 Giessen, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Bunde
mesh_terms: D001426:Bacterial Proteins; D042541:Intracellular Space / Q000378:metabolism; D013058:Mass Spectrometry; D008958:Models, Molecular; D015233:Models, Statistical; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D059748:Proteolysis; D012372:ROC Curve; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D010446:Peptide Fragments; D011506:Proteins