Modeling and validation of L-asparaginase enzyme, an anticancer agent using the tools of computational biology

Abstract

Background: The L-Asparaginase is a medically important drug. The L-Asparaginase enzyme, an anticancer agent produced by microorganisms is used for the treatment of patients suffering from lymphoma and leukemia. The L-Asparaginase is economical and its administration is easy when compared to other commercial drugs available in market. Many microbes have been reported to produce the L-Asparaginase.Methods: In the present work the sequence of L-Asparaginase enzyme protein was obtained from the Universal Protein Resource (UNIPROT) server. The sequence of L-Asparaginase was used to generate 3-D model of L-Asparaginase in SWISS MODEL server. The constructed L-Asparaginase model was verified using Ramachandran Plot in PROCHECK server.Results: The FASTA format of L-Asparaginase enzyme of Bacillus subtilis strain 168 was retrieved from UNIPROT server. The FASTA format of L-Asparaginase was submitted to SWISS MODEL and its three-dimensional structural model was developed based on relevant template model. The model structure of L-Asparaginase was validated in PROCHECK server using Ramachandran Plot. The Ramachandran Plot of L-Asparaginase model inferred the reliability of L-Asparaginase structure model developed in SWISS MODEL server.  Conclusions: In the present study computational tools were exploited to develop and validate a potent anticancer drug, L-Asparaginase. Further the modeled L-Asparaginase enzyme protein can be improved using advanced bioinformatics tools and the same improved enzyme can be produced by improving the L-Asparaginase producing microbial strains by site-directed mutagenesis in the corresponding gene.