在罗塞塔种植甘氨酸:准确的de novo甘氨酸建模,密度匹配和合理的序列设计
Jared Adolf-Bryfogle1,2,3,4,5, Jason W Labonte6, John C Kraft7,8
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.
PLoS computational biology
|June 24, 2024
概括
我们开发了GlycanTreeModeler,这是一种精确预测和设计复杂碳水化合物结构的计算工具. 这种算法有助于确定糖蛋白结构,并使得新的应用,如用于疫苗设计的糖掩饰.
科学领域:
- 结构生物学 结构生物学
- 计算化学计算化学
- 葡萄糖科学 (Glycoscience) 是一种科学.
背景情况:
- 碳水化合物和糖蛋白对生物功能至关重要,但它们的复杂结构很难通过实验来确定.
- 计算方法为预测,确定和设计碳水化合物结构提供了一个有希望的途径.
研究的目的:
- 开发一种新的甘建模算法,GlycanTreeModeler,用于精确的计算预测和碳水化合物结构的设计.
- 将GlycanTreeModeler应用于设计用于特定应用的甘氨酸,例如在疫苗开发中进行屏蔽.
主要方法:
- 开发了GlycanTreeModeler,这是一个层次的糖构建算法.
- 使用基于蛋白质数据库 (PDB) 和量子力学 (QM) 数据的自适应内核密度估计 (KDE).
- 在不同的甘氨酸结构上对该算法进行了基准测试,并将其应用于新的建模和密度导向建筑.
主要成果:
- 甘氨酸TreeModeler在预测本地甘氨酸结构方面表现出很高的准确性.
- 该算法成功执行了新的建模和实验密度引导建筑.
- 为蛋白质纳米粒子疫苗设计了de novo glycan树来实现抗体屏蔽,并通过实验验证.
结论:
- GlycanTreeModeler是一款用于准确预测和设计甘氨酸结构的强大工具.
- 开发的计算方法可以为糖蛋白建模和糖掩盖策略提供信息.
- 这项工作推进了用于实验性结构确定和复杂碳水化合物的精制的计算方法.
相关概念视频
01:25Protein Glycosylation
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
01:24Oligosaccharide Assembly
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
01:05Proteoglycans
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...