What is LigBuilder V3?

    LigBuilder V3 is a multiple-purposed program developed for structure-based de novo drug design and optimization. Based on the three-dimensional structure of the target protein, it can automatically build ligand molecules within the binding pocket and subsequently screen them. Main purpose of LigBuilder V3 include:

    Cavity module:

    (1) Detecting and analyzing the ligand-binding site of the target protein.

    (2) Estimating the drugabbility of binding site.

    (3) Generating receptor-based pharmacophore model.

    Build module:

    (1) de novo design. Generating ligands with high ligand efficiency and novety.

    (2) Lead optimization.Optimizing given lead fragments to improve the activity.

    (3) Fragments linking. Finding ways of linkage for given fragments to integrate active fragments into a single compound.

    (4) Mimic design. Generating novel compounds that mimic the known inhibitor. (a) Automatically generating biased scoring funcion based on known inhibitors. (b) Automatically extracting key fragments from known inhibitors, and optimizing them with growing or linking strategy. (c) Drug-like hetro-ring replacing

    (5) User controlled design. LigBuilder could design specific compounds based on user's knowledge and intention

    (6) Multi-targets drug design. Designing single ligand that targeting multiple distinct receptor. Supporting all design modes, inluding de novo design, lead optimization and fragments linking.

    (7) Ligand analysis. (a) Protein-ligand binding affinity estimation (b) Filtering (c) Auto-recommendation (d) Synthesis analysis (e) Substructure Search. (f) Ligand clustering.

For more detailed description of LigBuilder V3, please refer to:

Yaxia Yuan; Jianfeng Pei; Luhua Lai, "LigBuilder 2: A Practical de Novo Drug Design Approach",J. Chem. Inf. Model., 2011, 51 (5), pp 1083–1091

And the reference of LigBuilder v1.2:

Wang, R.; Gao, Y.; Lai, L. "LigBuilder: A Multiple-Purpose Program for Structure-Based Drug Design", J.Mol.Model., 2000, 6, 498-516.

Click here to download the previous version of LigBuilder (version 1.2)

Applications of LigBuilder series:

Bhowmick S, Chorge RD, Jangam CS, Bharatrao LD, Patil PC, Chikhale RV, Islam MA. "Identification of potential cruzain inhibitors using de novo design, molecular docking and dynamics simulations studies". Journal of Biomolecular Structure and Dynamics. 2019:1-7.

Gutti G, Kumar D, Paliwal P, Ganeshpurkar A, Lahre K, Kumar A, Krishnamurthy S, Singh SK. "Development of pyrazole and spiropyrazoline analogs as multifunctional agents for treatment of Alzheimer’s disease". Bioorganic Chemistry. 2019:103080.

Pascoini AL, Federico LB, Arêas AL, Verde BA, Freitas PG, Camps I. "In silico development of new acetylcholinesterase inhibitors". Journal of Biomolecular Structure and Dynamics. 2019;37(4):1007-21.

Park H, Jung HY, Mah S, Hong S. "Systematic computational design and identification of low picomolar inhibitors of aurora kinase a". Journal of chemical information and modeling. 2018;58(3):700-9.

Marinou M, Platis D, Ataya FS, Chronopoulou E, Vlachakis D, Labrou NE. "Structure-based design and application of a nucleotide coenzyme mimetic ligand: Application to the affinity purification of nucleotide dependent enzymes". Journal of Chromatography A. 2018;1535:88-100.

Kesharwani RK, Singh DB, Singh DV, Misra K. "Computational study of curcumin analogues by targeting DNA topoisomerase II: a structure-based drug designing approach". Network Modeling Analysis in Health Informatics and Bioinformatics. 2018;7(1):15.

Gusman DH, Shoemake C. "Evaluation and Optimization of in silico designed Sphingosine-1-Phosphate (S1P) Receptor Subtype 1 Modulators for the Management of Multiple Sclerosis". The Yale journal of biology and medicine. 2017;90(1):15-23.

Park H, Shin Y, Kim J, Hong S. "Application of fragment-based de novo design to the discovery of selective picomolar inhibitors of glycogen synthase kinase-3 beta". Journal of medicinal chemistry. 2016;59(19):9018-34.

Bonavia S, Shoemake C. "Design and optimisation of novel Huperzine A analogues capable of modulating the acetylcholinesterase receptor for the management of Alzheimers disease". Journal of Pharmacognosy and Phytotherapy. 2016 May 31;8(5):99-108.

Park H, Shin Y, Choe H, Hong S. "Computational design and discovery of nanomolar inhibitors of IκB kinase β". Journal of the American Chemical Society. 2015 Jan 2;137(1):337-48.

Kumar R, Pal K, Pal A. "In Silico Drug Designing of HIV-1 Reverse Transcriptase Inhibitors". The International Journal of Science and Technoledge. 2015 May 1;3(5):192.

Portelli G, Shoemake CM. "The Design and Optimisation of Novel Human Dihydrofolate Reductase Inhibitors for the Management of Proliferative Disease". Biomirror. 2015 Sep 1;6(9).

Park H, Lee S, Hong S. "Structure-based de novo design and synthesis of aminothiazole-based p38 MAP kinase inhibitors". Bioorganic & medicinal chemistry letters. 2015 Sep 15;25(18):3784-7.

Shang E, Yuan Y, Chen X, Liu Y, Pei J, Lai L. ”De novo design of multitarget ligands with an iterative fragment-growing strategy“. Journal of chemical information and modeling. 2014 ;54(4):1235-41.

Manara M, Shoemake C, Sant Fournier M. "Dipeptidylpeptidase-4 Enzyme Inhibitors: A de novo Design and Optimization Study of Novel Lead Molecules Containing a Deazaxanthine Scaffold". Biomirror. 2014;5(9).

Kare P, Bhat J, Sobhia ME. "Structure-based design and analysis of MAO-B inhibitors for Parkinson’s disease: using in silico approaches". Molecular diversity. 2013;17(1):111-22.

Park H, Hong S, Kim J, Hong S. "Discovery of picomolar ABL kinase inhibitors equipotent for wild type and T315I mutant via structure-based de novo design". Journal of the American Chemical Society. 2013 May 24;135(22):8227-37.

Vivek D. "Insilico Drug Designing of Potent Inhibitors for PDE7B, A Therapeutic Target for Leukemia". Research Journal of Pharmaceutical Sciences. 2012 Sep;1(1):10-5.

Vlachakis D, Tsagrasoulis D, Megalooikonomou V, Kossida S. "Introducing Drugster: a comprehensive and fully integrated drug design, lead and structure optimization toolkit". Bioinformatics. 2012;29(1):126-8.

Park H, Jeong Y, Hong S. "Structure-based de novo design and biochemical evaluation of novel BRAF kinase inhibitors". Bioorganic & medicinal chemistry letters. 2012;22(2):1027-30.

Agnihotri S, Narula R, Joshi K, Rana S, Singh M. "In silico modeling of ligand molecule for non structural 3 (NS3) protein target of flaviviruses". Bioinformation. 2012;8(3):123.

Omer A, Prasad CS. "Designing allosteric modulators for active conformational state of m-glutamate G-protein coupled receptors". Bioinformation. 2012;8(4):170.

Thakur PK, Hassan MI. "Discovering a potent small molecule inhibitor for gankyrin using de novo drug design approach". International journal of computational biology and drug design. 2011 ;4(4):373-86.

Jain S, Bari SB, Namdeo R. "Denovo design and optimization of novel inhibitor molecules for HIV integrase". International Journal of ChemTech Research. 2011;3:716.

Pareek H, Thakur P, Ray D. Modeling and docking studies of 4-aminobutyrate aminotransferase for huntington’s disease. Int. J. Pharma Bio Sci. 2011;2:539-49.

Jitendra S, Vinay R. "Structure based drug designing of a novel antiflaviviral inhibitor for nonstructural 3 protein". Bioinformation. 2011;6(2):57.

Park H, Bahn YJ, Ryu SE. "Structure-based de novo design and biochemical evaluation of novel Cdc25 phosphatase inhibitors". Bioorganic & medicinal chemistry letters. 2009 Aug 1;19(15):4330-4.

Singh N, Misra K. "Computational screening of molecular targets in Plasmodium for novel non resistant anti-malarial drugs". Bioinformation. 2009;3(6):255.

Kandil S, Biondaro S, Vlachakis D, Cummins AC, Coluccia A, Berry C, Leyssen P, Neyts J, Brancale A. "Discovery of a novel HCV helicase inhibitor by a de novo drug design approach". Bioorganic & medicinal chemistry letters. 2009;19(11):2935-7.

Shuaishuai Ni, Yaxia Yuan, Jin Huang, etc. "Discovering Potent Small Molecule Inhibitors of Cyclophilin A Using de Novo Drug Design Approach", J. Med. Chem. 2009, 52, 5295–5298

Jaganatharaja J, Gowthaman R. "Computational screening of inhibitors for HIV-1 integrase using a receptor based pharmacophore model". Bioinformation. 2006;1(4):112.

Tondel K, Drablos F. "Design of selective inhibitors of tyrosine kinase 2". Letters in Drug Design & Discovery. 2005;2(7):507-15.

Zhang XW, Yap YL, Altmeyer RM. "Generation of predictive pharmacophore model for SARS-coronavirus main proteinase". European journal of medicinal chemistry. 2005;40(1):57-62.

Yates AS, Doughty SW, Kendall DA, Kellam B. "Chemical modification of the naphthoyl 3-position of JWH-015: in search of a fluorescent probe to the cannabinoid CB2 receptor". Bioorganic & medicinal chemistry letters. 2005;15(16):3758-62

    LigBuilder V3 is written in ANSI C++ and has been tested on LINUX platforms. OpenBabel was called directly to convert molecules to SVG format and generating FP2 fingerprint, so an OpenBabel version 2.3.0 or later should be installed first. And, you may need graphical molecular modeling software to prepare the input files and check the resultant molecules.

    The LigBuilder V3 program is developed by Yaxia Yuan based on the previous version LigBuilder v1.2 developed by Dr. Renxiao Wang. Copyright of the LigBuilder V3 program belongs to the Institute of Physical Chemistry, Peking University, China.

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(These web pages are edited by Yaxia Yuan. Latest update: Jan, 2021)