已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Molecular analysis of dUTPase of Helicobacter pylori for identification of novel inhibitors using in silico studies

生物信息学 计算生物学 小分子 虚拟筛选 幽门螺杆菌 药物发现 人口 化学 对接(动物) 结合位点 蛋白质-蛋白质相互作用 生物 生物化学 遗传学 基因 社会学 人口学 护理部 医学
作者
Rinki Sisodia,Debapriyo Sarmadhikari,P.A. Mazumdar,Shailendra Asthana,Chaithanya Madhurantakam
出处
期刊:Journal of Biomolecular Structure & Dynamics [Taylor & Francis]
卷期号:: 1-26 被引量:1
标识
DOI:10.1080/07391102.2023.2247080
摘要

The human gastric pathogen Helicobacter pylori chronically affects the gastric mucosal layer of approximately half of world's population. The emergence of resistant strains urges the need for identification of novel and selective drug against new molecular targets. A ubiquitous enzyme, Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase), is considered as first line of defense against uracil mis-incorporation into DNA, and essential for genome integrity. Lack of dUTPase triggers an elevated recombination frequency, DNA breaks and ultimately cell death. Hence, dUTPase can be considered as a promising target for development of novel lead inhibitor compounds in H. pylori treatment. Herein, we report the generation of three-dimensional model of the target protein using comparative modelling and its validation. To identify dUTPase inhibitors, a high throughput virtual screening approach utilizing Knowledge-based inhibitors and DrugBank database was implemented. Top ranked compounds were scrutinized based on investigations of the protein-ligand interaction fingerprints, molecular interaction maps and binding affinities and the drug potentiality. The best ligands were studied further for complex stability and intermolecular interaction profiling with respect to time under 100 ns classical molecular dynamic stimulation, establishing significant stability in dynamic states as observed from RMSD and RMSF parameters and interactions with the catalytic site residues. The binding free energy calculation computed using MM-GBSA method from the MD simulation trajectories demonstrated that our molecules possess strong binding affinity towards the Helicobacter pylori dUTPase protein. We conclude that our proposed molecules may be potential lead molecules for effective inhibition against the H. pylori dUTPase protein subject to experimental validation.Communicated by Ramaswamy H. Sarma.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
大模型应助小燕子采纳,获得10
3秒前
斯文的萧完成签到,获得积分10
3秒前
十四发布了新的文献求助10
4秒前
直觉发布了新的文献求助10
5秒前
5秒前
7秒前
小蘑菇应助漂亮白枫采纳,获得10
8秒前
Hello应助漂亮白枫采纳,获得10
8秒前
李健应助欣慰的剑鬼采纳,获得10
8秒前
小刘发布了新的文献求助10
10秒前
13秒前
14秒前
张昭蓉完成签到 ,获得积分10
15秒前
miles发布了新的文献求助10
19秒前
Hello应助猪蹄采纳,获得10
19秒前
顾众生发布了新的文献求助10
21秒前
21秒前
天天快乐应助科研通管家采纳,获得10
24秒前
Jasper应助科研通管家采纳,获得10
24秒前
深情安青应助科研通管家采纳,获得10
24秒前
24秒前
大个应助科研通管家采纳,获得10
24秒前
27秒前
27秒前
nihao完成签到 ,获得积分10
29秒前
晶晶发布了新的文献求助10
30秒前
小燕子发布了新的文献求助10
32秒前
32秒前
大学生发布了新的文献求助10
33秒前
浮生若梦发布了新的文献求助10
35秒前
谨慎雪碧发布了新的文献求助10
35秒前
慎默应助酷炫的冰淇淋采纳,获得10
37秒前
Anthonywll完成签到 ,获得积分10
39秒前
Nicole完成签到 ,获得积分10
42秒前
43秒前
直觉发布了新的文献求助10
48秒前
51秒前
51秒前
领导范儿应助桀桀桀采纳,获得10
51秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
Aktuelle Entwicklungen in der linguistischen Forschung 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989868
求助须知:如何正确求助?哪些是违规求助? 3531994
关于积分的说明 11255752
捐赠科研通 3270793
什么是DOI,文献DOI怎么找? 1805053
邀请新用户注册赠送积分活动 882215
科研通“疑难数据库(出版商)”最低求助积分说明 809208