关键词: computer simulation molecular conformation molecular docking simulation molecular dynamics simulation obesity peptides

Mesh : Humans Obesity / drug therapy metabolism Animals Computer Simulation Molecular Docking Simulation Anti-Obesity Agents / pharmacology therapeutic use Lipase / metabolism antagonists & inhibitors Molecular Targeted Therapy / methods

来  源:   DOI:10.3390/ijms25094699   PDF(Pubmed)

Abstract:
In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question \"What therapeutic targets have been used in in silico analysis for the treatment of obesity?\" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an \"unclear risk of bias\" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity.
摘要:
在信息技术时代和可用的额外计算搜索工具和软件,本系统综述旨在确定肥胖的潜在治疗靶点,在计算机上进行评估,随后在体内进行验证。系统评价最初以研究问题“在肥胖的治疗中使用了哪些治疗目标?”为指导,并基于首字母缩写PECo(P,问题;E,曝光;公司,上下文)。根据系统审查和荟萃分析方案的首选报告项目清单(PRISMA-P),在PROSPERO(CRD42022353808)中制定并注册了系统审查方案。并遵循PRISMA进行系统审查。根据资格标准选择研究,与PECo结盟,在以下数据库中:PubMed,ScienceDirect,Scopus,WebofScience,BVS,和EMBASE。搜索策略产生了1142篇文章,从中,根据评估标准,系统评价中包括12个。只有七篇这些文章允许鉴定计算机和体内重新评估的治疗靶标。在这些目标中,五个完全是实验性的,一个完全是理论上的,其中一个目标呈现了实验部分和通过建模获得的部分。使用的主要方法是分子对接,研究最多的靶标是人胰脂肪酶(HPL)(n=4)。缺乏方法细节导致超过50%的论文在11个评估标准中有8个被归类为“不清楚的偏见风险”。从目前的系统评价来看,似乎很明显,将计算机方法整合到潜在药物靶标的研究中,以探索新的治疗剂提供了重要的工具,考虑到控制肥胖的持续挑战。
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