期刊
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
卷 115, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jmgm.2022.108228
关键词
Pharmacophore search; Pharmacophore comparison; K-means clustering; Virtual screening; Structure-based pharmacophore; Graph theory
A method using the K-means clustering algorithm to derive pharmacophore models of the binding site from fragment flooded X-ray protein structures was developed and validated by comparing with X-ray ligand structure-derived pharmacophores.
Discovering new hit small molecules binding to a specific protein binding site can be a difficult task. In support of existing procedures, a proof of concept methodology has been developed to process fragment flooded X-ray protein structures using the K-means clustering algorithm in order to derive pharmacophore models of the binding site. The novel method includes the implementation of several K-means initialisation methods in serial and parallel versions. Furthermore, required parameter optimisations for two initialisation methods was achieved, which was necessary to determine their validity and performance. A graph theory algorithm was adapted to compare the clustering-derived pharmacophores with X-ray ligand structure-derived pharmacophores to confirm that they mapped to each other. Initial proof of concept method validation was demonstrated using the Androgen Receptor (AR).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据