AUTHOR=Yuan Yaxia , Pei Jianfeng , Lai Luhua 

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

JOURNAL=Frontiers in Chemistry

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2020.00142

DOI=10.3389/fchem.2020.00142

ISSN=2296-2646

ABSTRACT=<p>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 <italic>de novo</italic> 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 <italic>de novo</italic> 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 <italic>de novo</italic> 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 “<ext-link ext-link-type="uri" xlink:href="http://www.pkumdl.cn/ligbuilder3/" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.pkumdl.cn/ligbuilder3/</ext-link>”.</p>