LigBuilder V3: A Multi-Target de novo Drug Design Approach

Yaxia Yuan, Jianfeng Pei, Luhua Lai

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


With the rapid development of systems-based pharmacology and poly-pharmacology, method development for rational design of multi-target drugs has becoming urgent. In this paper, we present the first de novo multi-target drug design program LigBuilder V3, which can be used to design ligands to target multiple receptors, multiple binding sites of one receptor, or various conformations of one receptor. LigBuilder V3 is generally applicable in de novo multi-target drug design and optimization, especially for the design of concise ligands for protein targets with large difference in binding sites. To demonstrate the utility of LigBuilder V3, we have used it to design dual-functional inhibitors targeting HIV protease and HIV reverse transcriptase with three different strategy, including multi-target de novo design, multi-target growing, and multi-target linking. The designed compounds were computational validated by MM/GBSA binding free energy estimation as highly potential multi-target inhibitors for both HIV protease and HIV reverse transcriptase. The LigBuilder V3 program can be downloaded at “”.

Original languageEnglish (US)
Article number142
JournalFrontiers in Chemistry
StatePublished - Feb 28 2020
Externally publishedYes


  • De novo design
  • Dual-functional inhibitors
  • LigBuilder
  • Multi-target drug design (MTDD)
  • multi-target drug optimization

ASJC Scopus subject areas

  • General Chemistry


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