Structure-Based Virtual Screening of Potential Hair-Care Compound Targeting Human Oxidosqualene Cyclase | IJCT Volume 13 – Issue 5 | IJCT-V13I5P57
International Journal of Computer Techniques
ISSN 2394-2231
Author
Dr. V. K. Singh
Abstract
The development of bioactive compounds for hair and scalp care increasingly incorporates structure-based computational approaches to identify molecules capable of interacting with proteins involved in lipid and sterol metabolism. Human oxidosqualene cyclase (OSC), also known as lanosterol synthase (LSS), catalyzes the cyclization of 2,3-oxidosqualene to lanosterol and represents an important enzyme in the cholesterol biosynthetic pathway. The availability of the experimentally determined three-dimensional structure of human OSC provides an opportunity for structure-based screening of small molecules. In the present study, a computational screening strategy was applied to identify compounds with potential affinity for human OSC and to explore their possible relevance to hair-care applications. The crystal structure of human OSC in complex with the reference inhibitor Ro 48-8071 was obtained from the Protein Data Bank under PDB accession 1W6J. The structure was determined by X-ray diffraction at 2.20 Å resolution. RCSB PDB A preliminary ligand-screening step was performed using BIOVIA Discovery Studio 2019 LibDock. From an initial collection of 37 selected molecules, 25 compounds available as three-dimensional SDF structures were subjected to the screening workflow. Subsequently, SwissDock 2024 was employed for molecular docking and comparative evaluation of the selected compounds against human OSC. SwissDock 2024 incorporates Attracting Cavities 2.0 and AutoDock Vina-based docking approaches and provides automated ligand and target preparation and pose ranking. The computational screening identified Tocopherols (PubChem CID 14986) as a prominent candidate when compared with the reference OSC inhibitor Ro 48-8071 (CID 1949). Tocopherols are recognized for antioxidant activity and use as cosmetic ingredients with antioxidant and skin-conditioning functions. The docking outcome suggests that Tocopherols can occupy a favorable region within the OSC binding environment and act as a potential OSC-interacting molecule for hair care. The present in silico screening study identifies Tocopherols (CID 14986) as a computationally promising candidate for further investigation against human OSC. The findings provide a structure-based hypothesis linking tocopherol chemistry with potential modulation of a sterol-biosynthetic target relevant to cellular lipid homeostasis. Experimental biochemical, cellular, formulation, and hair-follicle studies are required to determine whether the predicted interaction translates into a meaningful biological or cosmetic effect.
Keywords
oxidosqualene cyclase; lanosterol synthase; human OSC; LSS; molecular docking; virtual screening; LibDock; SwissDock; AutoDock Vina; tocopherol; vitamin E; hair care; computational drug discovery
Conclusion
The present study employed a structure-based computational workflow to screen potential compounds against human oxidosqualene cyclase (OSC), an important enzyme in the cholesterol biosynthetic pathway. The experimentally determined human OSC structure 1W6J, containing the known inhibitor Ro 48-8071, was selected as the structural target and reference system. An initial set of 37 selected molecules was narrowed to 25 compounds represented by three-dimensional SDF structures and screened using BIOVIA Discovery Studio 2019 LibDock. Subsequent molecular docking using SwissDock 2024 identified Tocopherols (PubChem CID 14986) as a prominent candidate in comparison with Ro 48-8071. The predicted interaction is particularly interesting because tocopherols possess substantial hydrophobic character and are already recognized for antioxidant and cosmetic applications. The findings therefore support Tocopherols as a candidate for further structure-based and experimental investigation against human OSC. However, the results should not be interpreted as evidence that Tocopherols inhibit OSC or promote hair growth until these effects have been experimentally confirmed. Tocopherols, commonly known as vitamin E compounds, are naturally occurring antioxidants found in several plant sources, particularly vegetable oils, nuts, seeds, and cereals. Important plant sources include sunflower seeds, soybean, corn, wheat germ, sesame, and almonds, which contain varying amounts of tocopherols. Based on your analysis, tocopherols can be described as beneficial ingredients for hair-care applications because of their antioxidant properties. They may help protect hair and scalp lipids from oxidative damage, support the conditioning properties of hair-care formulations, and contribute to maintaining healthy-looking hair. Therefore, tocopherol-rich plant oils or purified tocopherols can be incorporated into capsules, shampoos, conditioners, hair oils, serums, and other cosmetic formulations intended to nourish and protect the hair and scalp.
References
1.Thoma, R., Schulz-Gasch, T., D’Arcy, B., Benz, J., Aebi, J., Dehmlow, H., Hennig, M., Stihle, M., & Ruf, A. (2004). Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase. Nature, 432(7013), 118–122. https://doi.org/10.1038/nature02993
2.Bugnon, M., Röhrig, U. F., Goullieux, M., Perez, M. A. S., Daina, A., Michielin, O., & Zoete, V. (2024). SwissDock 2024: major enhancements for small-molecule docking with Attracting Cavities and AutoDock Vina. Nucleic acids research, 52(W1), W324–W332. https://doi.org/10.1093/nar/gkae300
3.Romano, M. T., Tafazzoli, A., Mattern, M., Sivalingam, S., Wolf, S., Rupp, A., Thiele, H., Altmüller, J., Nürnberg, P., Ellwanger, J., Gambon, R., Baumer, A., Kohlschmidt, N., Metze, D., Holdenrieder, S., Paus, R., Lütjohann, D., Frank, J., Geyer, M., Bertolini, M., … Betz, R. C. (2018). Bi-allelic Mutations in LSS, Encoding Lanosterol Synthase, Cause Autosomal-Recessive Hypotrichosis Simplex. American journal of human genetics, 103(5), 777–785. https://doi.org/10.1016/j.ajhg.2018.09.011
4.Duniec-Dmuchowski, Z., Fang, H. L., Strom, S. C., Ellis, E., Runge-Morris, M., & Kocarek, T. A. (2009). Human pregnane X receptor activation and CYP3A4/CYP2B6 induction by 2,3-oxidosqualene:lanosterol cyclase inhibition. Drug metabolism and disposition: the biological fate of chemicals, 37(4), 900–908. https://doi.org/10.1124/dmd.108.025130
5.Christianson D. W. (2017). Structural and Chemical Biology of Terpenoid Cyclases. Chemical reviews, 117(17), 11570–11648. https://doi.org/10.1021/acs.chemrev.7b00287
6.Romano, M. T., Tafazzoli, A., Mattern, M., Sivalingam, S., Wolf, S., Rupp, A., Thiele, H., Altmüller, J., Nürnberg, P., Ellwanger, J., Gambon, R., Baumer, A., Kohlschmidt, N., Metze, D., Holdenrieder, S., Paus, R., Lütjohann, D., Frank, J., Geyer, M., Bertolini, M., … Betz, R. C. (2018). Bi-allelic Mutations in LSS, Encoding Lanosterol Synthase, Cause Autosomal-Recessive Hypotrichosis Simplex. American journal of human genetics, 103(5), 777–785. https://doi.org/10.1016/j.ajhg.2018.09.011
7.Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N., & Bourne, P. E. (2000). The Protein Data Bank. Nucleic acids research, 28(1), 235–242. https://doi.org/10.1093/nar/28.1.235
8.Apweiler, R., Bairoch, A., Wu, C. H., Barker, W. C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M., Martin, M. J., Natale, D. A., O’Donovan, C., Redaschi, N., & Yeh, L. S. (2004). UniProt: the Universal Protein knowledgebase. Nucleic acids research, 32(Database issue), D115–D119. https://doi.org/10.1093/nar/gkh131
9.Kim, S., Thiessen, P. A., Bolton, E. E., Chen, J., Fu, G., Gindulyte, A., Han, L., He, J., He, S., Shoemaker, B. A., Wang, J., Yu, B., Zhang, J., & Bryant, S. H. (2016). PubChem Substance and Compound databases. Nucleic acids research, 44(D1), D1202–D1213. https://doi.org/10.1093/nar/gkv951
10.Diller, D. J., & Merz, K. M., Jr (2001). High throughput docking for library design and library prioritization. Proteins, 43(2), 113–124. https://doi.org/10.1002/1097-0134(20010501)43:2<113::aid-prot1023>3.0.co;2-t
11.Bugnon, M., Röhrig, U. F., Goullieux, M., Perez, M. A. S., Daina, A., Michielin, O., & Zoete, V. (2024). SwissDock 2024: major enhancements for small-molecule docking with Attracting Cavities and AutoDock Vina. Nucleic acids research, 52(W1), W324–W332. https://doi.org/10.1093/nar/gkae300
12.Wang, J., Cheng, Z., Yao, Q., Liu, L., Xu, D., & Hu, G. (2024). Bioinformatics and biomedical informatics with ChatGPT: Year one review. Quantitative biology (Beijing, China), 12(4), 345–359. https://doi.org/10.1002/qub2.67
13.Shue, E., Liu, L., Li, B., Feng, Z., Li, X., & Hu, G. (2023). Empowering beginners in bioinformatics with ChatGPT. Quantitative biology (Beijing, China), 11(2), 105–108. https://doi.org/10.15302/j-qb-023-0327
14.Xu D. (2023). ChatGPT opens a new door for bioinformatics. Quantitative biology (Beijing, China), 11(2), 204–206. https://doi.org/10.15302/j-qb-023-0328
Cinquin O. (2024). Steering veridical large language model analyses by correcting and enriching generated database queries: first steps toward ChatGPT bioinformatics. Briefings in bioinformatics, 26(1), bbaf045. https://doi.org/10.1093/bib/bbaf045
How to Cite This Paper
Dr. V. K. Singh (2026). Structure-Based Virtual Screening of Potential Hair-Care Compound Targeting Human Oxidosqualene Cyclase. International Journal of Computer Techniques, 13(5). ISSN: 2394-2231.
