Computational prediction of the effects of D57 to N57 substitution on RRM1 structure and function in the development of lung papillary adenocarcinoma and adenosquamous pancreas carcinoma

Abstract

Ribonucleotide reductase catalytic subunit M1 (RRM1) is a key component of an enzyme critical to DNA synthesis. Its expression has been associated with lung papillary adenocarcinoma and adenosquamous pancreas carcinoma. This study used computational methods to predict whether the D57N mutation in RRM1 contributes to the manifestation of these diseases. The structures of RRM1 ligands retrieved from nine (9) databases were docked with homology modeled wild type and mutant RRM1 using GRAMM-X Web Server v1.2. It had been assessed to be the most accurate among three docking software tested. The stability of the mutant complex was assessed by calculating the binding free energy change (??G). The computed ??G and the functions of the proteins suggest that twelve (12) proteins (PPP1CC, ATG5, COPS5, SGSH, CDK2, BMI1, RRM2, KAT5, CEP152, OTUB1, RNF2, and NTRK1) are involved in lung papillary adenocarcinoma and adenosquamous pancreas carcinoma.