Abstract

STRUCTURAL ANALYSIS AND BINDING PROPERTIES OF MODELED HUMAN SURFACTANT PROTEIN-A

Sivaprasad Mudili, Lubna Nousheen, Akkiraju.PavanChand, Surekharani Maddukuri , M.Srilakshmi, *Sreenivas.Enaganti

ABSTRACT

Surfactant protein A (SP-A) constitutes an important part of the innate immune defense in the lung. The three-dimensional (3D) model of the human surfactant protein-A (hSP-A) has been constructed based on the crystal structure of Rat norvegicus 1R13 protein (Protein Data Bank ID: 1R13) using MODELLER 9.9 software. Under the process of homology modeling 2 models were generated, and the model having the lowest modeler objective function value was chosen for further assessment. The generated model assessed and validated using PROCHECK, ProSA and RMSD that showed the final refined model is reliable, with 0.59 Ã… as RMSD and has -6.11 as Z-scores. Furthermore, with the generated model, we carried out binding studies with simple carbohydrate and lipid ligands using the Molegro Virtual Docker. Docking studies with these ligands into the active site of hSP-A indicate that maltose and Dipalmitoylphosphatidylcholine are more preferred ligands than others, with the binding scores of -93.8850 & -103.774 respectively. Docking studies revealed that Arg58, Arg63, Glu144, Lys34, Ser 98, Asp99, Glu33 and Ile59 of receptor are important determinant residues as they have strong hydrogen bonding contacts with both carbohydrate and lipid compounds. This is in good agreement with the experimental results. Results of the current study will provide a deep insight about the structure and function of Surfactant Protein-A and how these interactions influence the binding and neutralization of pulmonary pathogens.

Keywords: Surfactant Protein-A (SPA), Homology Modeling, Docking, Rattus norvegicus, Lipids, Carbohydrates.