Docking of Heparin 2S and 2SNS with 4C1 IDS Conformation Oligomer on FGF2-FGFR1 Terner Complex.
Barroroh, Himmatul,1,2, a) Harir, Fajrul,1, b) Hakim, Lukman, 2,c) Safitri, Anna, 2,d) And Widodo, Widodo 2, e)

1) UIN Maulana Malik Ibrahim Malang, Jl. Gajayana No.50 Malang, East Java, Indonesia, 65144.
2) Brawijaya University, Jl. Veteran Malang, East Java, Indonesia, 65144

Abstract

Based on clinical trial data, it seems that heparin has potential as an anticancer. Heparin is an oligosaccharide consisting of repeating units of glucosamine and iduronic acid. Heparin can have varying lengths of repeating units and sulfo groups attached to different positions. The iduronic acid in heparin can naturally be in the 2S0, 1C4 or 4C1 conformation. In this study, the potential and interaction of 2S and 2SNS heparin oligosaccharides with the iduronic conformation 4C1 with variations in length of 2-12 saccharide oligomers to FGF2-FGFR1 terner ligan-receptor complex will be studied by molecular docking using Autodock 4.2 with the default force field. The receptor suppose to be related to anticancer activity. This study aims to determine the preferential structure of the heparin-ligand-receptor complex, the interaction and the potential of the heparin length variation as an anticancer. Predictive test of heparin activity in preventing or inhibiting growth and spread (anti-neoplastic) in cancer used PassOnline. The stability of the docked complex structure was tested again by optimizing the docked structure on YASARA using the NOVA AMBER force field.
Docking results showed that the score of approximated binding energy of heparin 2SNS 3-7 saccharides has low energy, namely -16.19, -15.83, -17.02, -16.66, -15.64 kcal/mol, respectively, with the lowest being heparin 5 saccharides. . Heparin 5 saccharide 2S has the lowest energy of -16.48 kcal/mol. Amino acid interactions that affect heparin activity on FGFR1-FGF2 are Lys 26, Lys 135, Lys 160, Lys 163, Lys 172, Lys 175, Lys 177, Lys 207, Asn 27, Lys 125, Lys 119, Arg 120, Thr 173. The re-optimization of the complex structure resulting from the docking of heparin 2SNS 5 saccharides resulted in more stable energy, namely -128.1 kcal/mol and 2S 5 sacharide is -62.3 kcal/mol. The similarity of the pose of the heparin-ligand-receptor complex can be seen through the RMSD value of 2SNS 5 sacharides of 1.697471 against

Keywords: docking, heparin, FGF2, FGFR1

Topic: Computational Chemistry and Material Sciences