Homology Modeling, Molecular Dynamics Simulation and Essential Dynamics on Anopheles gambiae D7r1

The proteins produced by the saliva and salivary glands of blood sucking arthropods play a vital role in transmission of the infected parasite to host and interfere the parasitic life cycle. The structure prediction of D7r1 and its active site leads to inhibition of hemostasis and inflammation in the host. D7r1 is a member of D7-related (D7r) salivary gland proteins that interferes various aspects of host physiology. Considering the significance of a protein, three dimensional structure of D7r1 model was generated by homology modeling and validated by PROCHECK, ERRAT, Verify-3D, RAMPAGE and Q mean server. The predicted structure has 96.9% of residues in the most favored region of the Ramachandran plot. The sequence and structural alignment between D7r1 and template 2PQL reveals that similar active site residues such as Ile42, Arg43, Tyr45, His56, Met57, Val60, Phe131, and Met156 involved in binding pocket formation. Further, a molecular dynamics simulation study was performed to reveal the prolonged stability of D7r1 protein. The essential dynamics which include PCA and FEL analysis were used to evaluate the conformational stability of D7r1. This combined molecular dynamics simulation and essential dynamics were used to provide comprehensive information of D7r1 and its active site prediction gain insights into the development of novel lead molecules for disrupting host-seeking behavior of mosquitoes.