开发in silico分类模型,以确定与葡萄糖皮质体受体的结合亲和力
Mark Stanojević1, Marjan Vračko2, Marija Sollner Dolenc3
1Bisafe Doo, V Kladeh 11c, 1000, Ljubljana, Slovenia; University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia.
Chemosphere
|June 10, 2023
概括
这项研究开发了计算模型来预测与葡萄糖皮质体受体 (GR) 的化学结合. 这些模型精确地选潜在的内分泌干扰物,有助于优先考虑进一步测试的化学物质.
科学领域:
- 计算毒理学计算毒理学
- 内分泌学 在内分泌学.
- 化学信息学 化学信息学
背景情况:
- 通过葡萄糖皮质体受体 (GR) 作用的内分泌干扰化学物质 (EDC) 具有显著的兴趣.
- 有限的实验数据需要选和优先考虑化学品的in silico方法.
- 预测与GR的化学相互作用对于风险评估至关重要.
研究的目的:
- 开发和验证计算分类模型,用于预测与葡萄糖皮质体受体 (GR) 的化学结合亲和力.
- 选和优先考虑化学品的潜在内分泌干扰性质.
- 评估in silico方法对GR相互作用预测的有用性.
主要方法:
- 使用反传播人工神经网络 (CPANN) 方法进行分类.
- 采用了142个激动剂化合物和182个对抗剂化合物的数据集,用于对抗剂结合亲和度的预测.
- 用DRAGON描述符表示化学结构;主要成分分析用于集群.
主要成果:
- 分类模型通过交叉验证证明了高准确度预测GR激动剂 (85.7%) 和对抗剂 (78.9%) 的活性.
- 初步分析显示,使用主要成分方法,结合剂和非结合剂之间的分离较弱.
- 对于化学物质和GR相互作用,CPANN模型提供了均衡且准确的预测.
结论:
- 在 silico 方法,特别是 CPANN 模型,是有效的工具来预测与葡萄糖皮质体受体的化学结合亲和力.
- 这些模型可以准确地选和优先考虑潜在的内分泌干扰的化学物质.
- 开发的模型为指导化学安全评估中的实验研究提供了宝贵的资源.
相关概念视频
The Two-State Receptor Model
2.0K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
The binding affinity of a drug determines its interaction with...
2.0K
Ligand Binding Sites
12.9K
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...
12.9K
The Equilibrium Binding Constant and Binding Strength
13.0K
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:
13.0K
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
Structure-Activity Relationships and Drug Design
800
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
800
G Protein-coupled Receptors
12.3K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
12.3K


