Proteins are the core molecules behind every life activities. They are the functional part of every organisms with life. The outcome of every protein in a living organism is controlled by the DNA/GENEs. Variant proteins are expressed in the body in different situations in different quantities. Unusual of the amount of different proteins are considered to be the main indication of most of the genetic diseases. In the case of cancer, it is very clear that, a number of unusual proteins are produced in the body or the amount of some proteins gets increased. Pirh2 is one of the main proteins expressed in most of the lung cancer.
Through these preliminary studies, we tried to implement a structural function modification in the protein from the sequence alteration. For this, the Zinc finger CHY-type (ZF_CHY) domain of Pirh2 is allowed to get substituted with Tip60 (an inhibitor) protein sequence. We expect a change in the protein function in such a way that, the same protein can inhibit other cancer proteins also. For this, the altered protein structure is modeled by the software MODELLER. The modeled structures are minimized using NAMD with VEGAZZ. The structures are verified for stereochemistry, 3D features and conformations by various validation tools.
It is expected that the structural modification of a protein is more stable if it is done in the sequence level. This may give more stability to the altered protein in the highly dynamic body system. But here the biggest challenge in the future studies lies on the synthesis of these protein.
Work carried out by Girinath G. Pillai and Raji Pillai.
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