Complete genome-wide screening and subtractive genomic approach revealed new virulence factors, potential drug targets against bio-war pathogen Brucella melitensis 16M

被引：3

作者：

Pradeepkiran, Jangampalli Adi ^{[1
]}

Sainath, Sri Bhashyam ^{[2
,3
]}

Kumar, Konidala Kranthi ^{[1
]}

Bhaskar, Matcha ^{[1
]}

机构：

[1] Sri Venkateswara Univ, Dept Zool, Div Anim Biotechnol, Tirupati 517502, Andhra Pradesh, India

[2] Univ Porto, Ctr Interdisciplinar Invest Marinha & Ambiental, CIMAR CIIMAR, P-4100 Oporto, Portugal

[3] Vikrama Simhapuri Univ, Dept Biotechnol, Nellore, Andhra Pradesh, India

来源：

DRUG DESIGN DEVELOPMENT AND THERAPY | 2015年 / 9卷

关键词：

Brucella melitensis 16M; homology modeling; putative genes; structure based virtual screening; subtractive genomic approach; targets; BRUCELLA-MELITENSIS; SECONDARY STRUCTURE; RAPID IDENTIFICATION; STRUCTURE PREDICTION; CODING GENES; PROTEIN; SEQUENCE; ANNOTATION; PHYLOGENY; KNOWLEDGE;

D O I：

10.2147/DDDT.S76948

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Brucella melitensis 16M is a Gram-negative coccobacillus that infects both animals and humans. It causes a disease known as brucellosis, which is characterized by acute febrile illness in humans and causes abortions in livestock. To prevent and control brucellosis, identification of putative drug targets is crucial. The present study aimed to identify drug targets in B. melitensis 16M by using a subtractive genomic approach. We used available database repositories (Database of Essential Genes, Kyoto Encyclopedia of Genes and Genomes Automatic Annotation Server, and Kyoto Encyclopedia of Genes and Genomes) to identify putative genes that are nonhomologous to humans and essential for pathogen B. melitensis 16M. The results revealed that among 3 Mb genome size of pathogen, 53 putative characterized and 13 uncharacterized hypothetical genes were identified; further, from Basic Local Alignment Search Tool protein analysis, one hypothetical protein showed a close resemblance (50%) to Silicibacter pomeroyi DUF1285 family protein (2RE3). A further homology model of the target was constructed using MODELLER 9.12 and optimized through variable target function method by molecular dynamics optimization with simulating annealing. The stereochemical quality of the restrained model was evaluated by PROCHECK, VERIFY-3D, ERRAT, and WHATIF servers. Furthermore, structure-based virtual screening was carried out against the predicted active site of the respective protein using the glycerol structural analogs from the PubChem database. We identified five best inhibitors with strong affinities, stable interactions, and also with reliable drug-like properties. Hence, these leads might be used as the most effective inhibitors of modeled protein. The outcome of the present work of virtual screening of putative gene targets might facilitate design of potential drugs for better treatment against brucellosis.

引用

页码：1691 / 1706

页数：16