title: PON-Sol: prediction of effects of amino acid substitutions on protein solubility.
abstract: Solubility is one of the fundamental protein properties. It is of great interest because of its relevance to protein expression. Reduced solubility and protein aggregation are also associated with many diseases.
  
  
  
  We collected from literature the largest experimentally verified solubility affecting amino acid substitution (AAS) dataset and used it to train a predictor called PON-Sol. The predictor can distinguish both solubility decreasing and increasing variants from those not affecting solubility. PON-Sol has normalized correct prediction ratio of 0.491 on cross-validation and 0.432 for independent test set. The performance of the method was compared both to solubility and aggregation predictors and found to be superior. PON-Sol can be used for the prediction of effects of disease-related substitutions, effects on heterologous recombinant protein expression and enhanced crystallizability. One application is to investigate effects of all possible AASs in a protein to aid protein engineering.
  
  
  
  PON-Sol is freely available at http://structure.bmc.lu.se/PON-Sol The training and test data are available at http://structure.bmc.lu.se/VariBench/ponsol.php
  
  
  
  mauno.vihinen@med.lu.se
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Center for Systems Biology, School of Computer Science and Technology, Soochow University, Suzhou 215006, China and Department of Experimental Medical Science, Lund University, Lund SE 221 84, Sweden.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund SE 221 84, Sweden.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Niroula
authors.affiliation: Center for Systems Biology.
authors.forename: Bairong
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund SE 221 84, Sweden.
authors.forename: Mauno
authors.initials: M
authors.lastname: Vihinen
mesh_terms: D019943:Amino Acid Substitution; D019295:Computational Biology; D006801:Humans; D011506:Proteins / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D012984:Software; D012995:Solubility
chemical_list: D011506:Proteins