Investigation of novel chemical inhibitors of human lysosomal acid lipase: virtual screening and molecular docking studies

Comb Chem High Throughput Screen. 2014;17(5):473-82. doi: 10.2174/1386207317666140314093403.

Abstract

In the current study, identification of new potent small inhibitors of human lysosomal acid lipase using structure-based methods has been reported. Virtual Screening (VS), compounds from literature and molecular docking studies were employed to find the suitable inhibitors against lysosomal acid lipase (LAL). Specifically for this study a homology model of LipA enzyme was generated based on the structure of dog gastric lipase. As a result of structurebased virtual screening 28 inhibitors were identified from ZINC database. Rest of the inhibitors were selected from literature. Among the studied 65 inhibitors, compound having zinc ID ZINC15707335 exhibiting minimum binding affinity and hydrogen bond and hydrophobic interactions with specific amino acid residues was selected as lead compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Databases, Pharmaceutical
  • Dogs
  • Drug Design*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Docking Simulation*
  • Molecular Sequence Data
  • Protein Binding
  • Sequence Alignment
  • Sterol Esterase / antagonists & inhibitors*
  • Sterol Esterase / chemistry
  • Sterol Esterase / metabolism

Substances

  • Enzyme Inhibitors
  • LIPA protein, human
  • Sterol Esterase