EVALUATION OF STRUCTURAL, MOLECULAR INTERACTION AND SIMULATION STUDY OF L-ASPARAGINASE OF Streptomyces koyangensis

A vital step in drug discovery is structural and interaction assessment. L-asparaginase is a highly used compound in various treatment regimens which includes combinational therapies. The application is not only limited to treating Acute lymphoblastic leukemia, where it is also found effective for myeloid leukemia and canine lymphoma. The study details about L-asparaginase of Streptomyces koyangensis (WP_203215894). Structural insights are obtained by evaluation with GalaxyTBM. The constructed 3D-model is based on L-asparaginase models belonging to Escherichia coli, Wolinella succinogenes and Helicobacter pylori. The Ramachandran assessment corresponds to 91.4% of residues in the favourable region while ProSA infers to -8.9 Z-score. Further, QMEAN4 score of -0.46, 92.903 ERRAT score as well as 100% of residues in agreement with Verify3D theory describe the quality of the protein to be good and acceptable. The protein is identified to be secreted in the cytoplasm as per subsequent CELLO version2.5. Docking studies involving L-asparaginase (WP_203215894) molecule with L-asparagine resulted in the lowest energy of -4.5 kcal/mol along with prominent active sites recognized by PyRx. Similar prediction in addition to -4.6 and -4.8 kcal/mol is also resulted by CB-Dock. Further, the binding conformation referring to affinity of -4.5 kcal/mol is also supported by the interpretation of GalaxySite with identification of the same residues involved in ligand interaction. High values of affinity correspond to the analysis by SwissDock referring to -9.42 kcal/mol. The RMSF plot generated as part of protein flexibility analysis by CABS flex 2.0 depicted varied fluctuations however, the crucial residues interacting with the ligand are computed to have RMSF value < 2 represents rigidity. The therapeutic effectiveness of the enzyme has created interest in terms of tracing prospective sources and conducting computational analysis. The anticipated structure of WP_203215894 and derived assumptions are helpful and contribute valuable information for future in-vitro findings on L-asparaginase.