期刊
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
卷 40, 期 3, 页码 1064-1073出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2020.1821782
关键词
Comparative modelling; molecular dynamics; cyanobacteria; lectin; microvirin
资金
- Fundacao Amazonia de Amparo a Estudos e Pesquisas do Para (FAPESPA) [ICAAF 099/2014]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [311686/2015-0]
This study improves the affinity interaction between cyanobacterial lectin microvirin and its ligand through in silico modeling. The model suggests that residue Asn55 contributes the most to the interaction with Man alpha(1-2)Man.
Lectins that bind to HIV envelope glycoprotein can inhibit virus-cell fusion and be used for rational drug design. This paper presents the results of anin silicoapproach to improve affinity interaction between the cyanobacterial lectin microvirin and its ligand Man alpha(1-2)Man. Comparative modeling and molecular dynamics tools were used. Additionally, the alanine scanning webserver was used to study the importance of protein residues in the binding site and to guide mutant production. The model obtained presented two homologous domains designated as domains A and B, each consisting of a single strand with triple and antiparallel beta-sheets of (beta 1-beta 3 and beta 6-beta 8). Disulfide bonds between the cysteines (Cys60-Cys80, Cys63-Cys78 and Cys8-Cys24) were also found. The highly conserved binding site, including residues Asn44, Ile45, Asp46, Gln54, Asn55, Glu58, Thr59, Gln81, Thr82 and Met83. The RMSD values of the di-mannose and the interaction site were very stable during the molecular dynamics. Calculations of the occupation time of the hydrogen bonds were made for the residues that showed interaction in the complex lectin and ligand. The residue that contributed most to the interaction with Man alpha(1-2)Man was Asn55. After validation, the model generated remained stable during the entire simulation. Despite its structural similarity with the template we used, our mutant (Thr82Arg) showed a higher affinity interaction with Man alpha(1-2)Man. Communicated by Ramaswamy H. Sarma
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