Surfactant Protein Essay

1457 words - 6 pages

Surfactant protein-D (SP-D) is a C-type lectin which is synthesized in various parts of the body. SP-D plays a key role in the auto immune disorders, lung infections and also helpful in the postnatal pregnancy. This also plays an active role in the host-defense mechanisms. In the host defense mechanism SP-D binds with various micro-organisms and other particles that enter the human body and act against them. In our present study we targeted on the interactions of surfactant protein –D with the lipid molecules where their interaction plays an important role in the defense mechanism. In our study lipid molecules were docked against the SP-D protein and interaction studies were carried-out. ...view middle of the document...

Lung tissue elasticity and structural integrity of the lungs is maintained by SP-D [1].It also has a special role in the tissue remodeling during pregnancy, but the specific role is unknown [2].
SP-D is a member of C-type lectins of the collectin family [3-5].Surfactant proteins are the combination of lipids and proteins which help in protecting the alveoli during the respiration process [6]. SP-D helps in the macrophage functioning and surfactant lipid homeostasis [7]. It binds to the surfactant proteins of specific type which in turn change their aggregation state and alters various particles presentation [8]. It binds to surfactant lipids immediately after being secreted and lyses the lipid membranes and converts them into the surfactant structures of smaller size which can be easily taken up by the alveolar cells [9-10]. Interaction of the SP-D with lipids and protein molecules of the various organisms plays a key role in the immune defense mechanism action against the microbes and the pathogens that enter the lungs during intake of the air.

In the present study we have studied the interaction of the surfactant protein –D with various lipid molecules. Here we have generated the site directed mutations at sites F335G [22] and R343V [21] in the protein molecules and studied the interaction of the lipids with the mutant and the wild protein molecules using the Discovery studio software. The hydrogen bond interactions of lipids with both wild and the mutant protein molecules were also studied.

Materials and methods:
Protein selection and preparation:
Protein molecule is selected from the swissprot database and the availability of the protein structure is verified. As the protein molecule have the structure, it is downloaded from the PDB database based on the highest resolution and the protein molecule is then prepared in the discovery studio by cleaning the protein molecule and applying the CHARMm force field.
Site-directed Mutagenesis:
Mutations were created in the protein molecule for the comparative study. Site-directed mutations were generated in the protein molecule using Build mutation parameter in Discovery Studio Software.
Protein preparation and Energy minimization:
Protein preparation was done using Discover Studio (DS), in which the protein molecule was cleaned first and then force field was applied. The energy of the molecule is then minimized. Energy minimization of the protein molecules is done by applying various minimization algorithms like steepest Descent, Conjugate gradient, Powell, Smart minimize [23]. Energy minimized protein molecule is used for the further study.
Ligand generation and optimization
The structure of lipid compounds, taken for binding analysis, is drawn by using Chemsketch. Further ligand preparation with constraint parameters such as ionization change, tautomer and isomer generation was done and all the duplicate structures are removed. 3D structure generation by catalyst algorithm is carried out in DS....

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