Statistical Analysis and Prediction of Covalent Ligand Targeted Cysteine   Residues

doi:10.1021/acs.jcim.7b00163

CORC > 北京大学 > 化学与分子工程学院

	Statistical Analysis and Prediction of Covalent Ligand Targeted Cysteine Residues
	Zhang, Weilin ; Pei, Jianfeng ; Lai, Luhua
刊名	JOURNAL OF CHEMICAL INFORMATION AND MODELING
	2017
关键词	AMINO-ACID ALPHABET PROTEIN DATA-BANK ALLOSTERIC DRUGS RATIONAL DESIGN BINDING-SITES DOCKING DISCOVERY IDENTIFICATION INHIBITORS INFORMATION
DOI	10.1021/acs.jcim.7b00163
英文摘要	Targeted covalent compounds or drugs have good potency as they can bind to a specific target for a Icing time with low doses. Most currently known covalent ligands were discovered by chance or by modifying existing non covalent compounds to make them covalently attached to a nearby reactive residue. Computational methods for novel covalent ligand binding prediction are highly demanded. We performed statistical analysis on protein complexes with covalent ligands attached to cysteine residues. We found that covalent modified cysteine residues have unique features compared to those not attached to covalent ligands, including lower pK(a), higher, exposure, and higher ligand binding affinity. SVM models were built to predict cysteine residues suitable for covalent ligand design with prediction accuracy of 0.73. Given a protein structure, our method can be used to automatically detect druggable cysteine residues for covalent ligand design, which is especially useful for identifying novel binding sites for covalent allosteric ligand design.; Ministry of Science and Technology [2016YFA0502303]; National Natural Science Foundation of China [21633001, 21673010]; SCI(E); ARTICLE; 6; 1453-1460; 57
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/473027]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Zhang, Weilin,Pei, Jianfeng,Lai, Luhua. Statistical Analysis and Prediction of Covalent Ligand Targeted Cysteine Residues[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2017.
APA	Zhang, Weilin,Pei, Jianfeng,&Lai, Luhua.(2017).Statistical Analysis and Prediction of Covalent Ligand Targeted Cysteine Residues.JOURNAL OF CHEMICAL INFORMATION AND MODELING.
MLA	Zhang, Weilin,et al."Statistical Analysis and Prediction of Covalent Ligand Targeted Cysteine Residues".JOURNAL OF CHEMICAL INFORMATION AND MODELING (2017).