Binding of lilrB2 and double-stranded Aβ(16-21)

doi:10.7523/j.ucas.2020.0031

Abstract

Abstract: LilrB2 is a kind of protein targeted by Aβ (1-42) oligomers. The binding of them may result in some symptoms related to Alzheimer’s disease. It’s important to explore the binding mechanisms for the design of inhibitors. Three different conformations were designed by molecular docking of lilrB2 and double-stranded Aβ (16-21), and were used as the initial conformations for molecular dynamics simulations. Three sets of data were analyzed, finding that the ASP23 residue on lilrB2 had a strong interaction with LYS residue on the chain of Aβ (16-21), which had an obvious effect on the binding of receptor and ligand. In different binding states, the interaction of CYS142 residue with VAL or PHE on the chain of Aβ (16-21) and the interaction of SER24 residue with ALA on the chain of Aβ (16-21) are favorable for the binding of receptor and ligand.

Key words: AD, molecular docking, molecular dynamics, binding mode

CLC Number:

O642

WU Wenze, LI Xiaoyi. Binding of lilrB2 and double-stranded Aβ(16-21)[J]. Journal of University of Chinese Academy of Sciences, 2022, 39(6): 727-731.

References

[1] Huang Y D, Mucke L. Alzheimer mechanisms and therapeutic strategies[J]. Cell, 2012, 148(6):1204-1222. DOI:10.1016/j.cell.2012.02.040.
[2] Sharma P, Srivastava P, Seth A, et al. Comprehensive review of mechanisms of pathogenesis involved in Alzheimer’s disease and potential therapeutic strategies[J]. Progress in Neurobiology, 2019, 174:53-89. DOI:10.1016/j.pneurobio.2018.12.006.
[3] Cao Q, Shin W S, Chan H, et al. Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design[J]. Nature Chemistry,2018,10(12):1213-1221. DOI:10.1038/s41557-018-0147-z.
[4] Kim T, Vidal G S, Djurisic M, et al. Human LilrB2 is a β-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer’s model[J]. Science, 2013, 341(6152):1399-1404. DOI:10.1126/science.1242077.
[5] Cerqueira N M F S A, Gesto D, Oliveira E F, et al. Receptor-based virtual screening protocol for drug discovery[J]. Archives of Biochemistry and Biophysics, 2015, 582: 56-67. DOI:10.1016/j.abb.2015.05.011.
[6] Nasica-Labouze J, Nguyen P H, Sterpone F, et al. Amyloid β protein and alzheimer’s disease: when computer simulations complement experimental studies[J]. Chemical Reviews, 2015, 115(9):3518-3563. DOI:10.1021/cr500638n.
[7] Warren G L, Do T D, Kelley B P, et al. Essential considerations for using protein-ligand structures in drug discovery[J]. Drug Discovery Today, 2012, 17(23-24):1270-1281. DOI:10.1016/j.drudis.2012.06.011.
[8] Zheng Y J, Tice C M, Singh S B. Conformational control in structure-based drug design[J]. Bioorganic & Medicinal Chemistry Letters, 2017, 27(13): 2825-2837. DOI:10.1016/j.bmcl.2017.04.079.
[9] 许叶春, 蒋华良. 老年痴呆相关蛋白靶标结构与功能关系的分子动力学模拟[J]. 中国科学院研究生院学报, 2009, 26(2):280-287. DOI: 10.7523/j.issn.2095-6134.2009.2.019.
[10] 方磊, 计明娟. PTP1B选择性抑制剂的分子动力学模拟及结合自由能计算[J]. 中国科学院研究生院学报, 2009, 26(1):58-64. DOI: 10.7523/j.issn.2095-6134.2009.1.009.
[11] Morris G M, Huey R, Lindstrom W, et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility[J]. Journal of Computational Chemistry, 2009, 30(16): 2785-2791. DOI:10.1002/jcc.21256.
[12] Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics[J]. Journal of Molecular Graphics, 1996, 14(1): 33-38. DOI:10.1016/0263-7855(96)00018-5.
[13] Phillips J C, Braun R, Wang W, et al. Scalable molecular dynamics with NAMD[J]. Journal of Computational Chemistry, 2005, 26(16): 1781-1802. DOI:10.1002/jcc.20289.
[14] MacKerell A D, Bashford D, Bellott M, et al. All atom empirical potential for molecular modeling and dynamics studies of proteins[J]. The Journal of Physical Chemistry. B, 1998, 102(18): 3586-3616. DOI:10.1021/jp973084f.
[15] Jorgensen W L, Chandrasekhar J, Madura J D, et al. Comparison of simple potential functions for simulating liquid water[J]. The Journal of Chemical Physics, 1983, 79(2): 926-935. DOI:10.1063/1.445869.