Molecular docking of polyether ether ketone and nano-hydroxyapatite in orthodontics

J. Pharm. Pharmacogn. Res., vol. 10, no. 4, pp. 676-686, July-August 2022.

Original Article

Molecular docking of polyether ether ketone and nano-hydroxyapatite as biomaterial candidates for orthodontic mini-implant fabrication

[Acoplamiento molecular de poliéter éter cetona y nano-hidroxiapatita como biomateriales candidatos para la fabricación de mini-implantes de ortodoncia]

I Gusti Aju Wahju Ardani1,2, Alexander Patera Nugraha1,2,3*, Monika Nilam Suryani1, Ryan Hafidz Putra Pamungkas1, Devani Githa Vitamamy1, Rizky Alif Susanto1, Riyanarto Sarno4, Aziz Fajar4, Viol Dhea Kharisma5, Albertus Putera Nugraha6, Tengku Natasha Eleena binti Tengku Ahmad Noor7,8

1Orthodontics Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Dental Implant Research Group, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Graduate Student of Dental Health Science, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

4Department of Informatics, Institut Teknologi Sepuluh Nopember, Surabaya, Indonesia.

5Department of Biology, Faculty of Mathematics and Natural Science, Universitas Brawijaya, Malang, Indonesia.

6Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

7Membership of Faculty of Dental Surgery, Royal College of Surgeons, Edinburgh University, United Kingdom.

8Malaysian Armed Forces Dental Officer, 609 Armed Forces Dental Clinic, Kem Semenggo, Kuching, Sarawak, Malaysia.



Context: Modified polyether ether ketone (PEEK) by adding nano-hydroxyapatite (HA) material on its fixture for mini-implant fabrication may increase resistance force through osseointegration.

Aims: To analyze the binding molecular docking of PEEK incorporated with HA as a biomaterial candidate for orthodontic mini-implant fabrication through a bioinformatic approach, an in silico study.

Methods: 3D ligand structure consisting of HA, PEEK and target proteins consisting of osteopontin, osteocalcin, osteonectin, bone morphogenetic protein 4 (BMP4), bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 7 (BMP7), alkaline phosphatase (ALP),  runt-related transcription factor 2 (RUNX2), Insulin growth factor-1 (IGF-1), osterix, tartrate-resistant acid phosphatase (TRAP), collagen alpha-1 (COL1A1) obtained from RCSB-PDB. It was analyzed the binding affinity of a single HA, PEEK, and HA + PEEK complex to twelve target proteins related to osseointegration. The types of chemical interactions produced by the ligands in the target protein domain consisted of Van der Waals, hydrogen, hydrophobic, pi, and alkyl.

Results: The blind docking simulation succeeded in identifying the most negative binding affinity; it was found in the HA + PEEK molecular complex compared to HA and PEEK in the single condition. The type of chemical interaction formed consisted of hydrogen, van der Waals, pi, and alkyl. HA+PEEK showed the most negative binding affinity with ALP and IGF-1, as much as -8.7 binding affinity.

Conclusions: The molecular docking of PEEK with HA exhibited a prominent binding affinity with osteogenic markers like ALP and IGF-1 in silico, allowing it to have a higher potential than nano-HA or PEEK as a single biomaterial for osseointegration as the fabrication of mini-implants that may support orthodontic treatment.

Keywords: dentistry; good health and well-being; in silico; medicine; temporary anchorage device.

This image has an empty alt attribute; its file name is jppres_pdf_free.png


Contexto: La poliéter éter cetona modificada (PEEK) puede aumentar la fuerza de resistencia a través de la osteointegración mediante la adición de material de nanohidroxiapatita (HA) para la fabricación de mini-implantes.

Objetivos: Analizar el acoplamiento molecular de PEEK incorporado con HA como candidato a biomaterial para la fabricación de miniimplantes de ortodoncia a través de un enfoque bioinformático, un estudio in silico.

Métodos: Estructura de ligando 3D que consiste en HA, PEEK y proteínas diana como osteopontina, osteocalcina, osteonectina, proteína morfogenética ósea 4 (BMP4), proteína morfogenética ósea 2 (BMP2), proteína morfogenética ósea 7 (BMP7), fosfatasa alcalina (ALP) , factor de transcripción relacionado con runt 2 (RUNX2), factor de crecimiento de insulina-1 (IGF-1), osterix, fosfatasa ácida tartrato resistente (TRAP), colágeno alfa-1 (COL1A1) obtenido de RCSB-PDB. Fue analizada la afinidad de unión del complejo único HA, PEEK y HA + PEEK a doce proteínas diana relacionadas con la osteointegración. Los tipos de interacciones químicas producidas por los ligandos en el dominio de la proteína objetivo consistieron en Van der Waals, hidrógeno, hidrofóbico, pi y alquilo.

Resultados: La simulación a ciegas de acoplamiento logró identificar la afinidad de unión más negativa. Esta se encontró en el complejo molecular HA + PEEK en comparación con HA y PEEK de forma individual. El tipo de interacción química formada consistió en hidrógeno, van der Waals, pi y alquilo. HA+PEEK mostró la afinidad de unión más negativa con ALP e IGF-1, con una afinidad de unión de -8,7.

Conclusiones: El acoplamiento molecular de PEEK con HA exhibió una afinidad de unión prominente con marcadores osteogénicos como ALP e IGF-1 in silico, lo que le permite tener un mayor potencial que HA o PEEK como biomaterial único para la osteointegración como la fabricación de mini-implantes que puedan soportar el tratamiento de ortodoncia.

Palabras Clave: buena salud y bienestar; dispositivo de anclaje temporal; in silico; odontología; medicina.

This image has an empty alt attribute; its file name is jppres_pdf_free.png

Citation Format: Ardani IGAW, Nugraha AP, Suryani NM, Pamungkas RH, Vitamamy DG, Susanto RA, Sarno R, Fajar A, Kharisma VD, Nugraha AP, Noor TNEBTA (2022) Molecular docking of polyether ether ketone and nano-hydroxyapatite as biomaterial candidates for orthodontic mini-implant fabrication. J Pharm Pharmacogn Res 10(4): 676–686.

Albrektsson T, Johansson C (2001) Osteoinduction, osteoconduction and osseointegration. Eur Spine J 10: S96–S101.

Alqahtani AR, Gufran K, Silva F, Rocha MG, Chang J (2021) A clinical case report of a potential acute allergic reaction with titanium dental implant. Case Rep Dent 2021: 5592934.

Antolis M, Anggani HS, Marshadianti D, Ayu D (2021) Mini implant orthodontic as an anchorage in skeletal class II malocclusion treatment with severe dental protrusion [Indonesian]. J Ked Gi Unpad 33(1):71–78.

Ardani IG, Rahmawati D, Narmada IB, Nugraha AP, Taftazani H, Kusumawardani MK (2020) Surface Electromyography unveil the relationship between masticatory muscle tone and maloclusion class I & II in Javanese ethnic patient. J Int Dent Med Res 13(4): 1447–1454.

Barkarmo S, Wennerberg A, Hoffman M, Kjellin P, Breding K, Handa P, Stenport V (2013) Nano-hydroxyapatite-coated PEEK implants: A pilot study in rabbit bone. J Biomed Mater Res Part A 101A(2): 465–471.

Cheng Z, Guo C, Dong W, He FM, Zhao SF, Yang GL (2012) Effect of thin nano-hydroxyapatite coating on implant osseointegration in ovariectomized rats. Oral Surg Oral Med Oral Pathol Oral Radiol 113(3): e48-e53.

Choi JW, Shin S, Lee CY, Lee J, Seo HH, Lim S, Lee S, Kim IK, Lee HB, Kim SW, Hwang KC (2017) Rapid induction of osteogenic markers in mesenchymal stem cells by adipose-derived stromal vascular fraction cells. Cell Physiol Biochem 44(1): 53–65.

de Oliveira PGFP, de Melo Soares MS, Silveira E Souza AMM (2021) Influence of nano-hydroxyapatite coating implants on gene expression of osteogenic markers and micro-CT parameters. An in vivo study in diabetic rats. J Biomed Mater Res A 109(5): 682–694.

Elias CN, Oliveira Ruellas AC, Fernandes DJ (2012) Orthodontic implants: Concepts for the orthodontic practitioner. Int J Dent 2012: 549761.

Geng YM, Ren DN, Li SY, Li ZY, Shen XQ, Yuan YY (2020) Hydroxyapatite-incorporation improves bone formation on endosseous PEEK implant in canine tibia. J Appl Biomater Funct Mater 18: 2280800020975172.

Gromolak S, Krawczenko A, Antończyk A, Buczak K, Kiełbowicz Z, Klimczak A (2020) Biological characteristics and osteogenic differentiation of ovine bone marrow derived mesenchymal stem cells stimulated with FGF-2 and BMP-2. Int J Mol Sci 21(24): 9726.

Guo T, Kang W, Xiao D, Duan R, Zhi W, Weng J (2013) Molecular docking characterization of a four-domain segment of human fibronectin encompassing the RGD loop with hydroxyapatite. Molecules 19(1): 149–158.

Gupitasari A, Putri LS (2018) The prevalence of bad habits as the etiology of angle’s class I malocclusion in orthodontic clinic dental hospital Jember in 2015-2016 [Indonesian]. Pus Kes 6(2): 365–370.

Hayman AR (2008) Tartrate-resistant acid phosphatase (TRAP) and the osteoclast/immune cell dichotomy. Autoimmunity 41(3):218-223.

Henry JP, Bordoni B (2021) Histology, Osteoblasts. In: StatPearls. Treasure Island (FL): StatPearls Publishing; Update May 10, 2021.

Herwanda H, Arifin R, Lindawati L (2016) Knowledge of adolescents age 15-17 at SMAN 4 Banda Aceh City on the side effects of using fixed orthodontic appliances  [Indonesian]. J Syiah Kuala Dent Soc 1(1): 79–84.

Jubhari EH, Dammar I, Launardo V, Goan Y (2020) Implant coating materials to increase osseointegration of dental implant: A systematic review. Sys Rev Pharm 11(12): 35–41.

Kazimierczak P, Przekora A (2020) Osteoconductive and osteoinductive surface modifications of biomaterials for bone regeneration: A concise review. Coatings 10(10): 971.

Kharisma VD, Ansori AN, Nugraha AP (2020) Computational study of ginger (Zingiber officinale) as E6 Inhibitor in human papillomavirus type 16 (HPV-16) infection. Biochem Cell Arch 20: 3155–3159.

Khotib J, Lasandara CSC, Samirah S, Budiatin AS (2019) Acceleration of bone fracture healing through the use of natural bovine hydroxyapatite implant on bone defect animal model. Fol Med Indones 55(33): 176-187.

Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, Han L, He J, He S, Shoemaker BA, Wang J (2016) PubChem Substance and Compound databases. Nucleic Acids Res 44(D1): D1202–D1213.

Levingstone TJ, Ardhaoui M, Benyounis K, Looney L, Stokes JT (2015) Plasma sprayed hydroxyapatite coatings: Understanding process relationships using design of experiment analysis. Surf Coat Technol 283: 29–36.

Loblobly M, Anindita PS, Leman MA (2015) Gambaran Maloklusi Berdasarkan Indeks Handicapping Malocclusion Assessment Record (HMAR) Pada Siswa SMAN 9 Manado [Indonesian]. e-GiGi 3(2): 625­–633.

Luqman A, Kharisma VD, Ruiz RA, Götz F (2020) In silico and in vitro study of trace amines (TA) and dopamine (DOP) interaction with human alpha 1-adrenergic receptor and the bacterial adrenergic receptor QseC. Cell Physiol Biochem 54(5): 888–898.

Ma Z, Zhao X, Zhao J, Zhao Z, Wang Q, Zhang C (2020) Biologically modified polyether ether ketone as dental implant material. Front Bioeng Biotechnol 8: 620537.

Megat Badarul Hisham PN, Narmada IB, Alida A, Rahmawati D, Nugraha A,  Putranti N (2019) Effects of vitamin D in alveolar bone remodeling on osteoblast numbers and bone alkaline phosphatase expression in pregnant rats during orthodontic tooth movement. J Orofac Sci 11(2): 79–83.

Mešić E, Muratović E, Redžepagić-Vražalica L, Pervan N, Muminović AJ, Delić M, Glušac M (2021) Experimental & fem analysis of orthodontic mini-implant design on primary stability. Appl Sci 11(12): 5461.

Najeeb S, Bds ZK, Bds SZ, Bds MS (2016) Bioactivity and osseointegration of PEEK are inferior to those of titanium: A systematic review. J Oral Implantol 42(6):512–516.

Naini A, Rubianto M, Latief FDE, Gunadi A, Kristiana D, Hendrijantini N (2020) Inflammatory and immunogenic response of the tissue after application of freeze-dried hydroxyapatite gypsum puger scaffold compared to freeze-dried hydroxyapatite bovine scaffold. Contemp Clin Dent 11(4): 371–375.

Nayak UK, Malviya N (2011) Role of mini-implants in orthodontics. Int J Oral Implantol Clin Res 2(3): 126–134.

Ntolou P, Tagkli A, Pepelassi E (2018) Factors related to the clinical application of orthodontic mini-implants. J Int Oral Health 10(3): 110.

Oka S, Li X, Zhang F (2020) MicroRNA-21 facilitates osteoblast activity. Biochem Biophys Rep 25: 100894.

Papathanasiou I, Kamposiora P, Papavasiliou G, Ferrari M (2020) The use of PEEK in digital prosthodontics: A narrative review. BMC Oral Health 20(1): 217.

Peng XB, Zhang Y, Wang YQ, He Q, Yu Q (2019) IGF-1 and BMP-7 synergistically stimulate articular cartilage repairing in the rabbit knees by improving chondrogenic differentiation of bone-marrow mesenchymal stem cells. J Cell Biochem 120(4): 5570–5582.

Prahasanti C, Nugraha AP, Kharisma VD, Ansori AN, Devijanti R, Ridwan TP, Ramadhani NF, Narmada IB, Ardani IG, Noor TN (2021) A bioinformatic approach of hydroxyapatite and polymethylmethacrylate composite exploration as dental implant biomaterial. J Pharm Pharmacogn Res 9(5): 746–754.

Prahasanti C, Nugraha AP, Saskianti T, Suardita K, Riawan W, Ernawat DS (2020) Exfoliated human deciduous tooth stem cells incorporating carbonate apatite scaffold enhance BMP-2, BMP-7 and attenuate MMP-8 expression duringinitial alveolar bone remodeling in Wistar rats (Rattus norvegicus). Clin Cosmet Investig Dent 12: 79–85.

Purnama YHC, Mastutik G, Putra ST (2018) Increased activity of mature osteoblast from rat bone marrow mesenchymal stem cells in osteogenic medium exposed to melatonin. Fol Med Indones 54(4): 282–288.

Ramadhani NF, Nugraha AP, Rahmadani D, Puspitaningrum MS, Rizqianti Y, Kharisma VD, Noor TNEBTA, Ridwan RD, Ernawati DS, Nugraha AP (2022) Anthocyanin, tartaric acid, ascorbic acid of roselle flower (Hibiscus sabdariffa L.) for immunomodulatory adjuvant therapy in oral manifestation coronavirus disease-19: An immunoinformatic approach. J Pharm Pharmacogn Res 10(3): 418–428.

Rose PW, Prlić A, Altunkaya A, Bi C, Bradley AR, Christie CH, Costanzo LD, Duarte JM, Dutta S, Feng Z, Green RK (2017) The RCSB protein data bank: Integrative view of protein, gene and 3D structural information. Nucleic Acids Res 45(D1): D271–D281.

Samirah, Budiatin AS, Mahyudin F, Khotib J (2021) Fabrication and characterization of bovine hydroxyapatite-gelatin-alendronate scaffold cross-linked by glutaraldehyde for bone regeneration. J Basic Clin Physiol Pharmacol 32(4): 555–560.

Sheoran L, Kumar P, Kumar S, Ulla ST, Hussain F (2021) Implants in orthodontics: A brief review. IP Indian J Orthod Dentofacial Res 7(1): 45–48.

Simangunsong S, Muttaqin Z, Tampubolon IA (2018) Description of malocclusion in Batak students based on dental aesthetic index [Indonesian]. Prima JODS 1(1): 40–48.

Sitasari PI, Narmada IB, Hamid T, Triwardhani A, Nugraha AP, Rahmawati D (2020) East Java green tea methanolic extractcan enhance RUNX2 and osterixexpression during orthodontic tooth movement in vivo. J Pharm Pharmacogn Res 8(4): 290–298.

Syada AN, Kurniawan FK, Wibowo D (2017) Comparison of severity levels and levels of orthodontic treatment needs using the malalignment index overview in junior high schools that have school health units and junior high schools that do not have UKS [Indonesian]. Jur Ked Gigi 2(1): 78–83.

Wang X, Mei L, Jiang X, Jin M, Xu Y, Li J, Li X, Meng Z, Zhu J, Wu F (2021) Hydroxyapatite-coated titanium by micro-arc oxidation and steam-hydrothermal treatment promotes osseointegration. Front Bioeng Biotechnol 9: 625877.

Valenti MT, Dalle Carbonare L, Mottes M (2016) Osteogenic differentiation in healthy and pathological conditions. Int J Mol Sci 18(1): 41.

Vieira-Andrade RG, Paiva S, Marques LS (2015) Impact of malocclusions on quality of life from childhood to adulthood. Iss Contemp Orthod 3: 39–55.

Zhou M, Geng YM, Li SY, Yang XB, Che YJ, Pathak JL, Wu G (2019) Nanocrystalline hydroxyapatite-based scaffold adsorbs and gives sustained release of osteoinductive growth factor and facilitates bone regeneration in mice ectopic model. Journal of Nanomaterials 2019: 1202159.

Zogheib T, Walter-Solana A, De la Iglesia F, Espinar E, Gil J, Puigdollers A (2021) Do titanium mini-implants have the same quality of finishing and degree of contamination before and after different manipulations? An in vitro study. Metals 11(2): 245.

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)