title: Computational biotechnology: prediction of competitive substrate inhibition of enzymes by buffer compounds with protein-ligand docking.
abstract: In vitro enzymatic activity highly depends on the reaction medium. One of the most important parameters is the buffer used to keep the pH stable. The buffering compound prevents a severe pH-change and therefore a possible denaturation of the enzyme. However buffer agents can also have negative effects on the enzymatic activity, such as competitive substrate inhibition. We assess this effect with a computational approach based on a protein-ligand docking method and the HYDE scoring function. Our method predicts competitive binding of the buffer compound to the active site of the enzyme. Using data from literature and new experimental data, the procedure is evaluated on nine different enzymatic reactions. The method predicts buffer-enzyme interactions and is able to score these interactions with the correct trend of enzymatic activities. Using the new method, possible buffers can be selected or discarded prior to laboratory experiments.
authors.affiliation: ZBH, Center for Bioinformatics, Universität Hamburg, Hamburg, Germany.
authors.forename: Karen T
authors.initials: KT
authors.lastname: Schomburg
authors.forename: Inés
authors.initials: I
authors.lastname: Ardao
authors.forename: Katharina
authors.initials: K
authors.lastname: Götz
authors.forename: Fabian
authors.initials: F
authors.lastname: Rieckenberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Liese
authors.forename: An-Ping
authors.initials: AP
authors.lastname: Zeng
authors.forename: Matthias
authors.initials: M
authors.lastname: Rarey
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry*; D001667:Binding, Competitive; D002021:Buffers; D019295:Computational Biology / Q000379:methods; D006597:Fructose-Bisphosphatase / Q000737:chemistry*; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry*; D005954:Glucosephosphate Dehydrogenase / Q000737:chemistry*; D008024:Ligands
chemical_list: D002021:Buffers; D008024:Ligands; D000426:Alcohol Dehydrogenase; C052370:1,3-propanediol dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D006597:Fructose-Bisphosphatase; D005956:Glucose-6-Phosphate Isomerase