Pharmacophore and structure-based drug design, molecular dynamics and admet/tox studies to design novel potential pad4 inhibitors

被引：29

作者：

Barcellos, Mariana P. ^{[1
]}

Santos, Cleydson B. R. ^{[2
]}

Federico, Leonardo B. ^{[1
]}

de Almeida, Paulo Fernando ^{[3
]}

de Paula da Silva, Carlos H. T. ^{[1
]}

Taft, Carlton A. ^{[4
]}

机构：

[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP, Brazil

[2] Univ Fed Amapa, Lab Modelagem & Quim Comp, Rod JK Km 2, BR-68902280 Macapa, AP, Brazil

[3] Univ Fed Bahia, Inst Ciencias Saude, Dept Ciencias Biointeracao, Av Reitor Miguel Calmon S-N, BR-40300100 Salvador, BA, Brazil

[4] CBPF, Rua Dr Xavier Sigaud 150, BR-22290180 Rio De Janeiro, RJ, Brazil

来源：

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS | 2019年 / 37卷 / 04期

关键词：

structure-based drug design; pharmacophore; molecular dynamics; Pad4; ADME/Tox; INTERACTION FIELD; IDENTIFICATION; PREDICTIONS; DOCKING;

D O I：

10.1080/07391102.2018.1444511

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have used docking (GLIDE), pharmacophore modeling (Discovery Studio), long trajectory molecular dynamics (Discovery Studio) and ADMET/Tox (QikProp and DEREK) to investigate PAD4 in order to determine potential novel inhibitors and hits. We have carried out virtual screening in the ZINC natural compounds database. Pharmacokinetics and Toxicity of the best hits were assessed using databases implemented in softwares that create models based on chemical structures taking into account consideration about the toxicophoric groups. A wide variety of pharmaceutical relevant properties are determined in order to make decisions about molecular suitability. After screening and analysis, the 6 most promising PAD4 inhibitors are suggested, with strong interactions (pi-stacking, hydrogen bonds, hydrophobic contacts) and suitable pharmacotherapeutic profile as well.

引用

页码：966 / 981

页数：16

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