title: An Integrated In Silico Approach for the Structural and Functional Exploration of Lipocalin 2 and its Functional Insights with Metalloproteinase 9 and Lipoprotein Receptor-Related Protein 2.
abstract: Recent evidence demonstrated that Lipocalin 2 (LCN2) is garnering interest from a wide spectrum as biomarker. Here, we present an in silico characterization of LCN2 belonging to prominent organisms focusing for their physicochemical and structural differences. We found significant variations in physicochemical properties between organisms and low sequence similarity based on their amino acid properties alone. However, we identified three main structurally distinct motif regions that are conserved among all variants. Further investigation was carried out to understand the functional insights of LCN2. We selected LCN2 sequence from Gallus gallus as an input query to identify unique scoring-framework based on computational tools and confidence scores of various putative associations. Among all ten proteins associated with LCN2; highest confidence of prediction were seen for the associations between LCN2 and metalloproteinase 9 (MMP9) and lipoprotein receptor-related protein 2 (LRP2) which play vital roles in tumor growth and iron transportation, respectively. We attempted to determine binding affinities of LCN2 with MMP9 and LRP2 through molecular modeling and docking. Selected docked models were examined for complex stability by GROMACS. Alteration of binding affinity between LCN2 with MMP9 and LRP2 proteins that we found in this study may provide new direction for future therapeutic targets.
authors: Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju Do, 690-756, Republic of Korea.
authors: Mrinmoy
authors: M
authors: Ghosh
authors: Simrinder Singh
authors: SS
authors: Sodhi
authors: Jeong Hyun
authors: JH
authors: Kim
authors: Nam Eun
authors: NE
authors: Kim
authors: Raj Kumar
authors: RK
authors: Mongre
authors: Neelesh
authors: N
authors: Sharma
authors: Sung-Woo
authors: SW
authors: Kim
authors: Sung Jong
authors: SJ
authors: Oh
authors: Krishna Kanth
authors: KK
authors: Pulicherla
authors: Dong Kee
authors: DK
authors: Jeong
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002645:Chickens; D003198:Computer Simulation; D017124:Conserved Sequence; D006801:Humans; D008024:Ligands; D054834:Lipocalins / Q000737:chemistry* / Q000378:metabolism*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010802:Phylogeny; D025941:Protein Interaction Mapping; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D008024:Ligands; D054834:Lipocalins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D020780:Matrix Metalloproteinase 9