LigBuilder 2: A Practical de Novo Drug Design Approach

被引：144

作者：

Yuan, Yaxia ^{[1
,2
]}

Pei, Jianfeng ^{[1
]}

Lai, Luhua ^{[1
,2
]}

机构：

[1] Peking Univ, Acad Adv Interdisciplinary Studies, Ctr Theoret Biol, Beijing 100871, Peoples R China

[2] Peking Univ, State Key Lab Struct Chem Unstable & Stable Speci, Coll Chem & Mol Engn, BNLMS, Beijing 100871, Peoples R China

来源：

JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2011年 / 51卷 / 05期

基金：

中国国家自然科学基金;

关键词：

MOLECULAR ARCHITECTURES; BINDING-SITES; LIGAND DESIGN; INHIBITORS; PROGRAM; COMBINATORIAL; GENERATION; DISCOVERY; RECEPTOR; DATABASE;

D O I：

10.1021/ci100350u

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have developed a new version (2.0) of the de novo drug design program LigBuilder. With LigBuilder 2.0, the synthesis accessibility of designed compounds can be analyzed, and a cavity detection procedure is implemented to detect the positions and shapes of the binding sites on the surface of a given protein structure and to quantitatively estimate drugability. Ligands are designed to best fit the detected cavities using a set of rules for evaluation. Drug-like and privileged fragments are used to construct the ligands with the aid of internal and external absorption, distribution, metabolism, excretion, and toxicity (ADME/T) and drug-like filters.

引用

页码：1083 / 1091

页数：9

共 35 条

[1] DESIGN, SYNTHESIS AND X-RAY CRYSTALLOGRAPHIC STUDIES OF NOVEL FKBP-12 LIGANDS
BABINE, RE
BLECKMAN, TM
KISSINGER, CR
SHOWALTER, R
PELLETIER, LA
LEWIS, C
TUCKER, K
MOOMAW, E
PARGE, HE
VILLAFRANCA, JE
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (15) : 1719 - 1724
[2] Structure and reaction based evaluation of synthetic accessibility
Boda, Krisztina
Seidel, Thomas
Gasteiger, Johann
[J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2007, 21 (06) : 311 - 325
[3] MULTIPLE HIGHLY DIVERSE STRUCTURES COMPLEMENTARY TO ENZYME BINDING-SITES - RESULTS OF EXTENSIVE APPLICATION OF A DE-NOVO DESIGN METHOD INCORPORATING COMBINATORIAL GROWTH
BOHACEK, RS
MCMARTIN, C
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (13) : 5560 - 5571
[4] THE COMPUTER-PROGRAM LUDI - A NEW METHOD FOR THE DENOVO DESIGN OF ENZYME-INHIBITORS
BOHM, HJ
[J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1992, 6 (01) : 61 - 78
[5] A novel binding pocket of cyclin-dependent kinase 2
Chen, Hao
Van Duyne, Rachel
Zhang, Naigong
Kashanchi, Fatah
Zeng, Chen
[J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2009, 74 (01) : 122 - 132
[6] Pocket v.2: Further developments on receptor-based pharmacophore modeling
Chen, Jing
Lai, Luhua
[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2006, 46 (06) : 2684 - 2691
[7] PRO-LIGAND - AN APPROACH TO DE-NOVO MOLECULAR DESIGN .1. APPLICATION TO THE DESIGN OF ORGANIC-MOLECULES
CLARK, DE
FRENKEL, D
LEVY, SA
LI, J
MURRAY, CW
ROBSON, B
WASZKOWYCZ, B
WESTHEAD, DR
[J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1995, 9 (01) : 13 - 32
[8] HOOK - A PROGRAM FOR FINDING NOVEL MOLECULAR ARCHITECTURES THAT SATISFY THE CHEMICAL AND STERIC REQUIREMENTS OF A MACROMOLECULE BINDING-SITE
EISEN, MB
WILEY, DC
KARPLUS, M
HUBBARD, RE
[J]. PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1994, 19 (03): : 199 - 221
[9] Fischer E., 1895, BER DTSCH CHEM GES, V28, P3252, DOI DOI 10.1002/CBER.189502803176
[10] A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases
Ghose, AK
Viswanadhan, VN
Wendoloski, JJ
[J]. JOURNAL OF COMBINATORIAL CHEMISTRY, 1999, 1 (01): : 55 - 68

← 1 2 3 4 →