TY - JOUR T1 - An AP Endonuclease 1–DNA Polymerase β Complex: Theoretical Prediction of Interacting Surfaces A1 - Abyzov, Alexej A1 - Uzun, Alper A1 - Strauss, Phyllis R. A1 - Ilyin, Valentin A. Y1 - 2008/04/25 N2 - Author SummaryOxidative damage to DNA happens in every cell as a consequence of the life process. Such damage can inhibit DNA replication and RNA transcription; if not repaired, it can lead to cancer. Consequently, all cells contain an important mechanism for identification and repair of oxidative lesions. Two proteins figure prominently: AP endonuclease 1, which cleaves the damaged site, and DNA polymerase beta, which inserts a new nucleotide to replace the damaged one. While several biochemical studies indicate interaction between the two proteins, the details of the interaction remain unknown. Here, we develop and apply a new methodology to predict the most likely protein-protein interface between the two proteins. The methodology relies on the assumption, which is validated by experimental evidence, that both proteins must bind to DNA in order to interact. Analysis of the simulated protein behavior in water allowed us to suggest how protein interaction might be coupled to conformational changes in DNA polymerase beta. Further comparative analysis identified coordinated mutations of specific residues at the predicted interfaces. This method can be applied to predict interaction details for any protein pair as long as the proteins in the pair are associated with DNA during the interaction. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 4 IS - 4 UR - https://doi.org/10.1371/journal.pcbi.1000066 SP - e1000066 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000066 ER -