Objective: Dynamic communication caused by mutation affects protein stability. The
main objective of this study is to explore how mutations affect communication and to provide
further insight into the relationship between heat resistance and signal propagation of Bacillus
subtilis lipase (Lip A).
Methods: The relationship between dynamic communication and Lip A thermostability is studied
by long-time MD simulation and residue interaction network. The Dijkstra algorithm is used to get
the shortest path of each residue pair. Subsequently, time-series frequent paths and spatio-temporal
frequent paths are mined through an Apriori-like algorithm.
Results: Time-series frequent paths show that the communication between residue pairs, both in
wild-type lipase (WTL) and mutant 6B, becomes chaotic with an increase in temperature; however,
more residues in 6B can maintain stable communication at high temperature, which may be
associated with the structural rigidity. Furthermore, spatio-temporal frequent paths reflect the
interactions among secondary structures. For WTL at 300K, β7, αC, αB, the longest loop, αA and αF
contact frequently. The 310-helix between β3 and αA is penetrated by spatio-temporal frequent paths.
At 400K, only αC can be frequently transmitted. For 6B, when at 300K, αA and αF are in more tight
contact by spatio-temporal frequent paths though I157M and N166Y. Moreover, the rigidity of the
active site His156 and the C-terminal of Lip A are increased, as reflected by the spatio-temporal
frequent paths. At 400K, αA and αF, 310-helix between β3 and αA, the longest loop, and the loop
where the active site Asp133 is located can still maintain stable communication.
Conclusion: From the perspective of residue dynamic communication, it is obviously found that
mutations cause changes in interactions between secondary structures and enhance the rigidity of
the structure, contributing to the thermal stability and functional activity of 6B.