Identification and evaluation of inhibitors of lipase from Malassezia restricta using virtual high-throughput screening and molecular dynamics studies

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

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 ofMrlip1. 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.

Original languageEnglish
Article number884
JournalInternational Journal of Molecular Sciences
Volume20
Issue number4
DOIs
Publication statusPublished - 2 Feb 2019
Externally publishedYes

Keywords

  • Anti-dandruff
  • Drug design and discovery
  • Lipase
  • Malassezia restricta
  • Molecular dynamics simulation
  • Traditional Chinese medicine
  • Zinc database

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