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Interaction of Glucagon G-Protein Coupled Receptor with Known Natural Antidiabetic Compounds: Multiscoring In Silico Approach.

Baig MH, Ahmad K, Hasan Q, Khan MK, Rao NS, Kamal MA, Choi I - Evid Based Complement Alternat Med (2015)

Bottom Line: Among all selected natural compounds, curcumin was found to be the most effective compound against GCGR followed by amorfrutin 1 and 4-hydroxyderricin.These compounds were rescored to confirm the accuracy of binding using another scoring function (x-score).The final conclusions were drawn based on the results obtained from the GOLD and x-score.

View Article: PubMed Central - PubMed

Affiliation: School of Biotechnology, Yeungnam University, Gyeongsan 712749, Republic of Korea.

ABSTRACT
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 effects is still a challenge to the medical system, and the search for a new and effective 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 effective compound against GCGR followed by amorfrutin 1 and 4-hydroxyderricin. These compounds were rescored to confirm the accuracy of binding using another scoring function (x-score). The final conclusions were drawn based on the results obtained from the GOLD and x-score. Further experiments were conducted to identify the atomic level interactions of selected compounds with GCGR.

No MeSH data available.


Related in: MedlinePlus

Change in total ASA of GCGR (uncomplexed and complexed).
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fig5: Change in total ASA of GCGR (uncomplexed and complexed).

Mentions: Changes in accessible surface area (ΔASA) in Å2 of the interacting residues of GCGR (uncomplexed) and in complex with curcumin, 4-hydroxyderricin, and amorfrutin 1 are shown in Tables 2 and 3. Changes in the total accessible surface area of GCGR before and after its interaction with the selected compounds were also calculated (Table 2). The results revealed that the uncomplexed GCGR had a total ASA of 18,930.488 Å2, which was reduced to 18,637.703, 18,661.982, and 18,674.038 Å2 after its complex formation with curcumin, 4-hydroxyderricin, and amorfrutin 1, respectively. This large change in the accessible surface area of GCGR provides solid evidence of the effectiveness of these selected compounds. Changes in the accessible surface area (ASA) in response to complex formation for each amino acid are shown in Table 3 and Figure 5. Many residues were found to have more than 10 Å2 of accessible surface area complex formation. For example, M231 had an ASA of 32.642 Å2, which decreased to 9.531, 0.767, and 9.363 Å2 after the binding of curcumin, 4-hydroxyderricin, and amorfrutin 1, respectively. Similar results were observed in the case of other active site residues (L307, V311, E362, V363, F365, and L386), which undergo a high reduction in ASA before and after binding of the selected natural compounds. This encompasses the small, standard, and large interface sizes as discussed by Conte et al. [43] and thus represents a good sampling of the space of protein interfaces.


Interaction of Glucagon G-Protein Coupled Receptor with Known Natural Antidiabetic Compounds: Multiscoring In Silico Approach.

Baig MH, Ahmad K, Hasan Q, Khan MK, Rao NS, Kamal MA, Choi I - Evid Based Complement Alternat Med (2015)

Change in total ASA of GCGR (uncomplexed and complexed).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4508340&req=5

fig5: Change in total ASA of GCGR (uncomplexed and complexed).
Mentions: Changes in accessible surface area (ΔASA) in Å2 of the interacting residues of GCGR (uncomplexed) and in complex with curcumin, 4-hydroxyderricin, and amorfrutin 1 are shown in Tables 2 and 3. Changes in the total accessible surface area of GCGR before and after its interaction with the selected compounds were also calculated (Table 2). The results revealed that the uncomplexed GCGR had a total ASA of 18,930.488 Å2, which was reduced to 18,637.703, 18,661.982, and 18,674.038 Å2 after its complex formation with curcumin, 4-hydroxyderricin, and amorfrutin 1, respectively. This large change in the accessible surface area of GCGR provides solid evidence of the effectiveness of these selected compounds. Changes in the accessible surface area (ASA) in response to complex formation for each amino acid are shown in Table 3 and Figure 5. Many residues were found to have more than 10 Å2 of accessible surface area complex formation. For example, M231 had an ASA of 32.642 Å2, which decreased to 9.531, 0.767, and 9.363 Å2 after the binding of curcumin, 4-hydroxyderricin, and amorfrutin 1, respectively. Similar results were observed in the case of other active site residues (L307, V311, E362, V363, F365, and L386), which undergo a high reduction in ASA before and after binding of the selected natural compounds. This encompasses the small, standard, and large interface sizes as discussed by Conte et al. [43] and thus represents a good sampling of the space of protein interfaces.

Bottom Line: Among all selected natural compounds, curcumin was found to be the most effective compound against GCGR followed by amorfrutin 1 and 4-hydroxyderricin.These compounds were rescored to confirm the accuracy of binding using another scoring function (x-score).The final conclusions were drawn based on the results obtained from the GOLD and x-score.

View Article: PubMed Central - PubMed

Affiliation: School of Biotechnology, Yeungnam University, Gyeongsan 712749, Republic of Korea.

ABSTRACT
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 effects is still a challenge to the medical system, and the search for a new and effective 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 effective compound against GCGR followed by amorfrutin 1 and 4-hydroxyderricin. These compounds were rescored to confirm the accuracy of binding using another scoring function (x-score). The final conclusions were drawn based on the results obtained from the GOLD and x-score. Further experiments were conducted to identify the atomic level interactions of selected compounds with GCGR.

No MeSH data available.


Related in: MedlinePlus