基于模板的昆虫气味受体建模优于AlphaFold3对连接体结合的预测
Amara Jabeen1, John Graham Oakeshott2, Siu Fai Lee2,3
1Applied BioSciences, Macquarie University, North Ryde, Sydney, NSW, 2109, Australia. amara.jabeen@mq.edu.au.
Scientific reports
|November 23, 2024
概括
基于模板的建模 (TBM) 和AlphaFold3 (AF3) 预测了昆虫气味受体 (OR) 的结构. TBM更好地预测OR-连接物的结合,为害虫控制研究提供了一个有前途的工具.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 计算化学的计算化学
背景情况:
- 昆虫利用气味受体 (ORs) 感知挥发性化合物,使它们成为害虫控制策略的关键目标.
- 对OR结构和功能的实验性确定具有挑战性,需要计算方法.
- 基于模板的建模 (TBM) 和AlphaFold3 (AF3) 是用于OR结构特征的新兴计算工具.
研究的目的:
- 评估TBM和AF3在预测昆虫OR结构和带结合模式方面的准确性.
- 为了比较TBM和AF3在预测OR-气味复合物的经验绑定数据中的有效性.
- 通过OR分析确定最适合通过OR分析推进害虫控制研究的计算方法.
主要方法:
- 使用TBM和AF3.3预测跳毛尾 OR (MhOR5) 的结构.
- 对已知的实验结构进行TBM和AF3预测的比较分析.
- 在*Bactrocera dorsalis*和*Bactrocera minax*的OR-气味复合物的模拟.
- 对结合亲和度,复杂稳定性和受体-连接体相互作用 (RLIs) 的评估.
主要成果:
- 无论是TBM还是AF3,都准确地预测了MhOR5的结构折叠,TBM在细胞外区域和连接体结合模式中显示出更高的准确性.
- 根据模拟后分析,TBM在区分OR气味剂结合剂和非结合剂方面表现优于AF3.
- TBM的卓越性能与基于疏水性的多重序列对齐 (MSA) 与保存的昆虫OR模板有关.
结论:
- 与AF3.3相比,TBM提供了更可靠的预测昆虫OR-连接体相互作用.
- 在TBM中的MSA方法有助于识别精制OR结构模型至关重要的保存残留物.
- TBM 是一个有价值的计算工具,用于推进对昆虫OR的研究,用于害虫控制应用.
相关概念视频
Ligand Binding Sites
12.7K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.7K
Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
The Equilibrium Binding Constant and Binding Strength
12.8K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
12.8K
Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K


