DRoP ‐ Detection of Related Solvent Positions

Conserved solvent binding sites are key features of protein structure and function. The Multiple Solvent Crystal Structures (MSCS) method uses organic solvent molecules to identify hot spots in protein‐ligand interactions. MSCS analysis of well studied enzymes shows clustering of organic solvent molecules primarily occurs in known binding sites. To date, detection of cluster sites has relied heavily on visual inspection, a time intensive process. In addition, a single cluster site can become dispersed in independently solved structures due to symmetry‐related positions. Here we present a semi‐automated method for the detection and analysis of conserved solvent sites. The Detection of Related Solvent Positions (DRoP) program detects and ranks cluster positions based on the degree of conservation. DRoP clustering of RNAse A from MSCS of two different crystal forms correctly identifies cluster sites. This program provides an efficient and consistent way to detect cluster sites, provides statistical data for clusters, and reports potential artificial cluster dispersion of both organic solvents and conserved crystallographic waters. The DRoP program is expected to be of general use for analysis of multiple structures in general.