ORIGINAL RESEARCH Homology modeling and docking studies of phosphoenolpyruvate carboxykinase in Schistosoma mansoni Ananta Swargiary • Akalesh Kumar Verma • Kishore Sarma Received: 18 April 2012 / Accepted: 20 October 2012 Ó Springer Science+Business Media New York 2012 Abstract Phosphoenolpyruvate carboxykinase (PEPCK) is an important catalytic enzyme in helminth parasites that catalyses a reverse reaction forming oxaloacetate from phosphoenolpyruvate. Because of its functional signifi- cance, present work was undertaken to construct and val- idate the 3D structure of PEPCK in Schistosoma mansoni. The 3D model protein was generated based on the known crystal structure of rat cytosolic PEPCK as template using Modeller 9v10 software. The resulting models were assessed by Procheck, Anolea, ProSA-web, and Errat. We have also identified all the pockets and voids on the best model protein to provide a detailed delineation of all atoms participating in their formation using CASTp server and to dock with best fitted ligand (guanosine diphosphate, GDP) using AutoDock 4.2. The model protein showed reliable structure with Ramachandran plot: 90.2 % core region, 9.1 % allow, 0.8 % generously allowed and 0.0 % disal- lowed region amino acid distributions. GDP was found to be docked in its active site, which formed a single H-bond with ASN 524 residue of model protein. Characterisation of PEPCK model protein has also been done to know its various biochemical natures. Therefore, the model structure could prove useful in further functional characterization and may be used to target and design drugs against S. mansoni. Keywords Schistosoma mansoni Á Phosphoenolpyruvate carboxykinase Á Homology modeling Á Docking Introduction Helminthiasis or helminthic infections remain to be one of the major health problems affecting billions of people all over the world (WHO, 2002, 2010). They are the most common infectious agents of human beings that contribute in the wide spread occurrence of undernourishment, ane- mia, eosinophilia and pneumonia (Bundy, 1994). A large number of commercial drugs including macrocyclic lac- tones, benzimidazoles, imidazothiazoles, and praziquantel are available in market to treat helminthic infections (McKellar and Jackson, 2004). But due to the lack of proper knowledge and understanding of physiology and biochemistry of parasitic helminths, use of many com- mercial anthelmintic drugs and its target on certain proteins become ineffective. Moreover, the development of drug resistance by helminth parasites is a big threat to effective control of helminthiasis. It has been seen that the synthesis of an effective novel drug against various diseases has always been a tedious process consuming several years, huge man power, and extremely expensive (Khan et al., 2011). Review of literature revealed that out of 1,556 new chemical entities marketed between 1975 and 2004, only few drugs like albendazole, oxamniquine, praziquantel, and ivermectin were successfully used to treat helminthiasis and found effective (Chirac and Torreele, 2006; Hotez, 2008). A clear understanding of the function and A. Swargiary (&) Parasitology Laboratory, Department of Zoology, North-Eastern Hill University, Shillong, India e-mail: ananta0183@gmail.com A. K. Verma Cell and Tumor Biology Laboratory, Department of Zoology, North-Eastern Hill University, Shillong, India K. Sarma West Bengal University of Technology, Kolkata, India 123 Med Chem Res DOI 10.1007/s00044-012-0289-2 MEDICINAL CHEMISTR Y RESEARCH