International Journal of Biochemistry and Biophysics 5(3): 65-77, 2017 http://www.hrpub.org DOI: 10.13189/ijbb.2017.050302 Homology Modeling, Molecular Dynamics Simulation and Essential Dynamics on Anopheles gambiae D7r1 Chayanika Goswami, Manikandan Jayraman, Tamizhmathi Bakthavachalam, Guneswar Sethi, Ramadas Krishna * Centre for Bioinformatics, School of Life Sciences, Pondicherry University, India Copyright©2017 by authors, all rights reserved. Authors agree that this article remains permanently open access under the terms of the Creative Commons Attribution License 4.0 International License Abstract 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. Keywords Anopheles gambiae, D7-related (D7r) Proteins, Homology Modeling, Molecular Dynamics Simulation, PCA and FEL Analysis 1. Introduction The blood feeding insects are responsible for transmitting a number of potentially lethal diseases like encephalitis, yellow fever and malaria (a most deadly tropical disease) are considered to be an important reason for socio-economic burden in developing countries [1]. In 2016, World Health Organization (WHO) reported the death of 438,000 people out of 214 million people with malarial infection. The deceased people were mainly children under the age of 5 [2]. The African mosquito Anopheles gambiae, carries the pathogen Plasmodium falciparum in their saliva and responsible for transmitting malaria to humans. The multi-drug resistance capability of Plasmodium parasites as well as resistance against chemotherapeutic agents makes it imperative to develop new anti-malarial drug agents [3]. Researchers are currently focused on developing new drugs and vaccines against the parasite. Till date, the most successful tactic to control malarial transmission to humans is found to be a reduction of the frequency of contact between the mosquito vectors and their human targets [4]. The African mosquito Anopheles gambiae is considered the best studied malarial parasite of Plasmodium falciparum and also plays a crucial role in the parasite life cycle. Approximately, 450 species of Anopheles mosquitoes are available worldwide, among them 60 species are reported to be a vector of human malaria [5]. Parasites are transmitted to humans once Anopheles mosquito bites and subsequently destroy red blood cells by multiplying in the host. Predominantly, female Anopheles gambiae mosquitos have an extremely high preference for feeding on humans. The selectivity of the female mosquito for human host is guided by olfactory responses to odor molecules that emanate from human skin and sweat [6]. The salivary gland of blood-feeding arthropods contains various potent bioactive substances essential for blood feeding. Several proteins produced by the salivary glands are significant for overcoming the problems caused by the host such as itch responses, immune defenses and homeostasis [7]. Further, it has been revealed that the pharmacological activity of arthropod salivary interrupts malarial pathogen transmission. Proteomic studies were performed on mosquito salivary gland proteins to define their imperative role on Plasmodium falciparum [8]. The identification of 67 proteins from Anopheles gambiae