在CASP16中建模替代的合规状态.
Namita Dube1, Theresa A Ramelot1, Tiburon L Benavides1
1Dept of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Sciences, Rensselaer Polytechnic Institute, Troy, New York, USA.
Proteins
|October 28, 2025
概括
CASP16实验显示了蛋白质建模的进步,但准确预测多个蛋白质和核酸状态仍然具有挑战性. 目前的方法与构造集团,特别是RNA和大型复合体,存在困难.
科学领域:
- 结构生物学 结构生物学
- 计算生物学 计算生物学
- 生物物理学的生物物理.
背景情况:
- 在CASP16集合预测实验中,评估了用于模拟多个构造状态中的分子的计算方法.
- 本研究的重点是实验确定结构的多州目标,不包括通过统计模型评估的域-链接器-域目标.
研究的目的:
- 评估各种结构状态中的蛋白质,核酸及其复合物的计算建模方面的进展.
- 在预测多态分子结构方面确定成功和持续的挑战.
主要方法:
- 十个多州目标被发布为社区挑战,包括连接体诱导的变化,蛋白质-DNA复合体和不同寡合体状态的RNA结构.
- 通过直接比较实验坐标来评估预测.
- 成功的方法通常涉及生成多个AlphaFold2模型,采用增强的采样和序列对齐,然后进行基于质量的选择.
主要成果:
- 对五个目标,特别是一个蛋白质-连接体复合体 (T1214) 实现了合理准确的模型 (TM-score > 0.75),使用一个apo结构作为模板.
- 预测者通常未能捕捉到国家之间的关键结构细节,除了T1214案例.
- 精度明显低于之前的CASP实验中单个状态目标的精度.
- 对于蛋白质-DNA复合体,RNA标和多重RNA寡合体状态的预测通常不足 (TM-score <0.75).
结论:
- 虽然已经取得了进展,但准确地建模形态组合,特别是对于RNA和大型多重体组合,仍然是一个重大挑战.
- 阿尔法Fold2和阿尔法Fold3显示出承诺,但个别组的表现各不相同,有时表现优于服务器.
- 多状态预测代表了结构生物学研究的重要前沿.
相关概念视频
02:02Chair Conformation of Cyclohexane
17.9K
The chair conformation is the most stable form of cyclohexane due to the absence of angle and torsional strain. The absence of angle strain is a result of cyclohexane’s bond angle being very close to the ideal tetrahedral bond angle of 109.5° in its chair conformer. Similarly, the torsional strain is also absent owing to the perfectly staggered arrangement of bonds.
The hydrogen atoms linked to carbons are arranged in two different axial and equatorial orientations to achieve this...
The hydrogen atoms linked to carbons are arranged in two different axial and equatorial orientations to achieve this...
17.9K
02:11Conformations of Cyclohexane
15.1K
Cyclohexane does not exist in a planar form due to the high angle and torsional strain it would experience in the planar structure. Instead, it adopts non-planar chair and boat conformations.
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...
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00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
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At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
1.2K
02:20Conformations of Butane
17.5K
Unlike ethane and propane that have only two major conformations, butane has more than two conformers. The staggered form of butane in which the bulky methyl groups on the two carbons are placed on opposite sides, that is, at a dihedral angle of 180°, is the lowest energy, most stable form — called the anti conformer. This conformation is stabilized due to the absence of steric repulsion between the largely spaced out methyl groups. The other two staggered conformations are...
17.5K
01:15¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR
1.7K
The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.
1.7K
02:18Conformations of Ethane and Propane
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In an organic molecule, free rotation about the carbon-carbon single bond results in energetically different conformers of the molecule. Due to this rotation, called the internal rotation, ethane has two major conformations — staggered and eclipsed.
Staggered conformation is a low energy and more stable conformation with the C-H bonds on the front carbon placed at 60°dihedral angles relative to the C-H bonds on the back carbon, leading to a reduced torsional strain. In staggered...
Staggered conformation is a low energy and more stable conformation with the C-H bonds on the front carbon placed at 60°dihedral angles relative to the C-H bonds on the back carbon, leading to a reduced torsional strain. In staggered...
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