Research Article Interaction of Glucagon G-Protein Coupled Receptor with Known Natural Antidiabetic Compounds: Multiscoring In Silico Approach M. H. Baig, 1 K. Ahmad, 2 Q. Hasan, 1 M. K. A. Khan, 3 N. S. Rao, 4 M. A. Kamal, 5,6 and I. Choi 1 1 School of Biotechnology, Yeungnam University, Gyeongsan 712749, Republic of Korea 2 Department of Biosciences, Integral University, Lucknow 226026, India 3 Department of Bioengineering, Integral University, Lucknow 226026, India 4 School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi 110067, India 5 King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia 6 Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770, Australia Correspondence should be addressed to M. H. Baig; mohdhassanbaig@gmail.com and I. Choi; inhochoi@ynu.ac.kr Received 24 April 2015; Accepted 15 June 2015 Academic Editor: Shreesh Ojha Copyright © 2015 M. H. Baig et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Glucagon receptor (GCGR) is a secretin-like (class B) family of G-protein coupled receptors (GPCRs) in humans that plays an important role in elevating the glucose concentration in blood and has thus become one of the promising therapeutic targets for treatment of type 2 diabetes mellitus. GCGR based inhibitors for the treatment of type 2 diabetes are either glucagon neutralizers or small molecular antagonists. Management of diabetes without any side efects is still a challenge to the medical system, and the search for a new and efective natural GCGR antagonist is an important area for the treatment of type 2 diabetes. In the present study, a number of natural compounds containing antidiabetic properties were selected from the literature and their binding potential against GCGR was determined using molecular docking and other in silico approaches. Among all selected natural compounds, curcumin was found to be the most efective compound against GCGR followed by amorfrutin 1 and 4-hydroxyderricin. hese compounds were rescored to conirm the accuracy of binding using another scoring function (-score). he inal conclusions were drawn based on the results obtained from the GOLD and -score. Further experiments were conducted to identify the atomic level interactions of selected compounds with GCGR. 1. Introduction Diabetes mellitus is a group of metabolic diseases in which the human body is unable to utilize and store available glucose, which results in the blood glucose level rising above the threshold level. Globally, diabetes has afected 347 million people to date [1]. he most common symptoms of this dis- ease include weight loss, polyuria, polydipsia, and polypha- gia [2]. Whenever glucose levels decrease in the blood (such as under fasting situations), glucagon-a 29-amino acid peptidal hormone is secreted by pancreatic -cells, which enhances the blood glucose level [3]. Increased glucagon in the blood leads to the promotion of glycogenolysis and gluconeogenesis in the liver, while the insulin inhibitory efect of these processes is attenuated, ultimately enhancing the blood glucose level [4]. he combined action of insulin and glucagon is required to maintain glucose homeostasis inside the body [5, 6]. herefore, two strategies have been applied to control diabetic hyperglycemia to date, reducing circulating glucagon levels and inhibiting glucagon mediated efects in target body tissues and cells. Several studies have demonstrated signiicant blood glucose lowering efects in diabetic animal models through application of potent peptide antagonists [7, 8], and immunoneutralization of glucagon in diabetic animals has been shown to reduce glucagon- stimulated hyperglycemia [9, 10]. Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2015, Article ID 497253, 6 pages http://dx.doi.org/10.1155/2015/497253