Community evolution and frequent subgraph patterns affect the thermostability of B. subtilis lipase A

Abstract Water-protein interactions are important for protein structure, function and thermal stability. In this study, based on the changes of the conformation of wild-type lipase (WTL) and its mutant (6B) at different temperatures over time, the residue-residue and residue-water networks and the residue-water hydrogen bond networks were constructed. The differences of community evolution between WTL and 6B were analyzed, and it was found that 6B has more stable communities, and the residues in the stable communities are mainly located in the loop and the C-termini of the highly flexible region, indicating that stabilizing the flexible regions are important for maintaining the three-dimensional structure of the protein. Through frequent subgraph mining, it was found that 6B has more stable residue-water hydrogen bonds. The residues located in loops and ɑ-helixes are more likely to form hydrogen bonds with water, and the hydrogen bonds between residues and water in ɑ-helixes are more stable than those in loops with the increase of temperature. Moreover, Glu20 and Asp111 after mutation are more likely to form stable hydrogen bonds with water, and the A20E and G111D mutations improved the structure of B. subtilis lipase A and enhanced its stability. It was also found that residues which can form hydrogen bonds with water frequently can also form stable interactions with residues.