Automatic detection of interacting carbonyl oxygens in peptide bond for the fragment molecular orbital method

Abstract The fragment molecular orbital (FMO) method has become an important tool in theoretical drug design and biophysical chemistry, as it enables detailed analysis of interactions among molecular fragments. However, interactions involving peptide bond carbonyl oxygens require particular attention, since the fragment molecular orbital fragmentation is not performed at the peptide bond, leading to shifts in residue assignment. Such inconsistencies can present difficulties not only for researchers new to fragment molecular orbital, but also for automated data processing. To address this issue, we have developed a Python-based script tool (named SARASA) that automatically detects and alerts residue shifts.