虚拟筛选和药效团设计新型巨噬细胞刺激因子理论抑制剂作为转移剂。
Virtual screening and pharmacophore design for a novel theoretical inhibitor of macrophage stimulating factor as a metastatic agent.
机构信息
Young Researchers and Elite Club, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
出版信息
Bioimpacts. 2013;3(3):141-4. doi: 10.5681/bi.2013.026. Epub 2013 Sep 21.
INTRODUCTION
Metastasis is a crucial aspect of cancer. Macrophage stimulating protein (MSP) is a single chain protein and can be cleaved by serum proteases. MSP has several roles in metastasis. In this in silico study, MSP as a metastatic agent was considered as a drug target.
METHODS
Crystallographic structure of MSP was retrieved from protein data bank. To find a chemical inhibitor of MSP, a library of KEGG compounds was screened and 1000 shape complemented ligands were retrieved with FindSite algorithm. Molegro Virtual Docker (MVD) software was used for docking simulation of shape complemented ligands against MSP. Moldock score was used as scoring function for virtual screening and potential inhibitors with more negative binding energy were obtained. PLANS scoring function was used for revaluation of virtual screening data.
RESULTS
The top found chemical had binding affinity of -183.55 based on MolDock score and equal to -66.733 PLANTs score to MSP structure.
CONCLUSION
Based on pharmacophore model of potential inhibitor, this study suggests that the chemical which was found in this research and its derivate can be used for subsequent laboratory studies.
简介
转移是癌症的一个关键方面。巨噬细胞刺激蛋白（MSP）是一种单链蛋白，可以被血清蛋白酶切割。MSP 在转移中具有多种作用。在这项计算机研究中，MSP 作为转移剂被视为药物靶点。
方法
从蛋白质数据库中检索 MSP 的晶体结构。为了找到 MSP 的化学抑制剂，筛选了 KEGG 化合物库，并使用 FindSite 算法检索了 1000 个形状互补配体。Molegro Virtual Docker (MVD) 软件用于针对 MSP 的形状互补配体对接模拟。Moldock 评分被用作虚拟筛选的评分函数，获得了具有更负结合能的潜在抑制剂。PLANS 评分函数用于重新评估虚拟筛选数据。
结果
根据 MolDock 评分，排名第一的化学物质与 MSP 结构的结合亲和力为-183.55，与 PLANTs 评分相等，为-66.733。
结论
基于潜在抑制剂的药效团模型，本研究表明，在这项研究中发现的化学物质及其衍生物可用于后续的实验室研究。
Zotero 插件