Dataset Information

Complex network analysis of thermostable mutants of Bacillus subtilis Lipase A.

ABSTRACT: Three-dimensional structures of proteins that regulate their functions can be modelled using complex network based approaches for understanding the structure-function relationship. The six mutants of the protein Lipase A from Bacillus subtilis, harbouring 2 to 12 mutations, retain their function at higher temperatures with negligible variation in their overall three-dimensional crystallographic structures. This enhanced thermostability of the mutants questions the structure-function paradigm. In this paper, a coarse-grained complex network approach is used to elucidate the structural basis of enhanced thermostability in the mutant proteins, by uncovering small but significant local changes distributed throughout the structure, rendering stability to the mutants at higher temperatures. Community structure analysis of the six mutant protein networks uncovers the specific reorganisations among the nodes/residues that occur, in absence of overall structural variations, which induce enhanced rigidity underlying the increased thermostability. This study offers a novel and significant application of complex network analysis that proposes to be useful in the understanding and designing of thermostable proteins.

SUBMITTER: Kandhari N

PROVIDER: S-EPMC6214246 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Complex network analysis of thermostable mutants of <i>Bacillus subtilis</i> Lipase A.

Kandhari Nitika N Sinha Somdatta S

Applied network science 20170626 1

Three-dimensional structures of proteins that regulate their functions can be modelled using complex network based approaches for understanding the structure-function relationship. The six mutants of the protein Lipase A from <i>Bacillus subtilis</i>, harbouring 2 to 12 mutations, retain their function at higher temperatures with negligible variation in their overall three-dimensional crystallographic structures. This enhanced thermostability of the mutants questions the structure-function parad ...[more]

PMID: 30443573

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Project description:Proteins in thermophilic organisms remain stable and function optimally at high temperatures. Owing to their important applicability in many industrial processes, such thermostable proteins have been studied extensively, and several structural factors attributed to their enhanced stability. How these factors render the emergent property of thermostability to proteins, even in situations where no significant changes occur in their three-dimensional structures in comparison to their mesophilic counter-parts, has remained an intriguing question. In this study we treat Lipase A from Bacillus subtilis and its six thermostable mutants in a unified manner and address the problem with a combined complex network-based analysis and molecular dynamic studies to find commonality in their properties. The Protein Contact Networks (PCN) of the wild-type and six mutant Lipase A structures developed at a mesoscopic scale were analyzed at global network and local node (residue) level using network parameters and community structure analysis. The comparative PCN analysis of all proteins pointed towards important role of specific residues in the enhanced thermostability. Network analysis results were corroborated with finer-scale molecular dynamics simulations at both room and high temperatures. Our results show that this combined approach at two scales can uncover small but important changes in the local conformations that add up to stabilize the protein structure in thermostable mutants, even when overall conformation differences among them are negligible. Our analysis not only supports the experimentally determined stabilizing factors, but also unveils the important role of contacts, distributed throughout the protein, that lead to thermostability. We propose that this combined mesoscopic-network and fine-grained molecular dynamics approach is a convenient and useful scheme not only to study allosteric changes leading to protein stability in the face of negligible over-all conformational changes due to mutations, but also in other molecular networks where change in function does not accompany significant change in the network structure.

Dataset Information

Complex network analysis of thermostable mutants of Bacillus subtilis Lipase A.

Publications

Complex network analysis of thermostable mutants of <i>Bacillus subtilis</i> Lipase A.

Similar Datasets

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