Identification and Evaluation of Inhibitors of Lipase from Malassezia restricta using Virtual High-Throughput Screening and Molecular Dynamics Studies

Ali, Shahid; Khan, Faez Iqbal; Mohammad, Taj; Lan, Dongming; Hassan, Md. Imtaiyaz; Wang, Yonghua

doi:10.3390/ijms20040884

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Identification and Evaluation of Inhibitors of Lipase from Malassezia restricta using Virtual High-Throughput Screening and Molecular Dynamics Studies

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School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China

Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi-110025, India

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2019, 20(4), 884; https://doi.org/10.3390/ijms20040884

Received: 28 December 2018 / Revised: 9 February 2019 / Accepted: 13 February 2019 / Published: 18 February 2019

(This article belongs to the Section Molecular Biophysics)

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Abstract

Recent studies revealed the role of lipase in the pathogenicity of Malassezia restricta in dandruff and seborrheic dermatitis (D/SD). The lipase from M. restricta (Mrlip1) is considered a potential target for dandruff therapy. In this work, we performed structure-based virtual screening in Zinc database to find the natural bioactive inhibitors of Mrlip1. We identified three compounds bearing superior affinity and specificity from the Traditional Chinese Medicine database (~60,000 compounds), and their binding patterns with Mrlip1 were analyzed in detail. Additionally, we performed three sets of 100 ns MD simulations of each complex in order to understand the interaction mechanism of Mrlip1 with known inhibitor RHC80267 and the newly identified compounds such as ZINC85530919, ZINC95914464 and ZINC85530320, respectively. These compounds bind to the active site cavity and cause conformational changes in Mrlip1. The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) studies suggested that the average binding energy was stronger in the case of Mrlip1-ZINC85530919 and Mrlip1-ZINC95914464. The selected natural inhibitors might act as promising lead drugs against Mrlip1. Further, the present study will contribute to various steps involved in developing and creating potent drugs for several skin diseases including dandruff. View Full-Text

Keywords: traditional Chinese medicine; lipase; Malassezia restricta; molecular dynamics simulation; anti-dandruff; Zinc database; drug design and discovery

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MDPI and ACS Style

Ali, S.; Khan, F.I.; Mohammad, T.; Lan, D.; Hassan, M.I.; Wang, Y. Identification and Evaluation of Inhibitors of Lipase from Malassezia restricta using Virtual High-Throughput Screening and Molecular Dynamics Studies. Int. J. Mol. Sci. 2019, 20, 884. https://doi.org/10.3390/ijms20040884

AMA Style

Ali S, Khan FI, Mohammad T, Lan D, Hassan MI, Wang Y. Identification and Evaluation of Inhibitors of Lipase from Malassezia restricta using Virtual High-Throughput Screening and Molecular Dynamics Studies. International Journal of Molecular Sciences. 2019; 20(4):884. https://doi.org/10.3390/ijms20040884

Chicago/Turabian Style

Ali, Shahid, Faez I. Khan, Taj Mohammad, Dongming Lan, Md. I. Hassan, and Yonghua Wang. 2019. "Identification and Evaluation of Inhibitors of Lipase from Malassezia restricta using Virtual High-Throughput Screening and Molecular Dynamics Studies" International Journal of Molecular Sciences 20, no. 4: 884. https://doi.org/10.3390/ijms20040884

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Identification and Evaluation of Inhibitors of Lipase from Malassezia restricta using Virtual High-Throughput Screening and Molecular Dynamics Studies

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