Why protein-structure confidence scores cannot substitute for a biological assay
蛋白质结构置信度分数无法完全替代生物测定，因为仅凭 FASTA 序列不足以完全指定蛋白质结构预测任务。单链、蛋白质组装体和蛋白质-配体复合物需要不同的输入和验证。数据库版本、比对、模板和采样协议也会改变实际测试结果。局部置信度、相对结构域位置和界面置信度等置信度分数关注预测几何的不同方面，但它们不测量催化活性或特定测定中的结合。关键在于评估输出支持何种生物学主张，以及在将模型选择的结构用于下游功能主张之前需要哪些证据。
- 发布
- 09/07 15:36 UTC+0
- 收录
- 09/08 00:00 UTC+0
- 来源类型
- 开发者社区
- 档位
- 社区
- 信源状态
- 正常
档位是按信源手工设定的编辑判断，不是逐条打分。
Disclosure: I run rewire.it, where I published the article linked below.
A FASTA sequence does not fully specify a protein-structure prediction job. A single chain, a protein assembly and a protein–ligand complex require different inputs and validation. Database versions, alignments, templates and the sampling protocol also change what was actually tested.
Confidence scores need the same distinction. Local confidence, relative domain placement and interface confidence concern different aspects of the predicted geometry. None is a measurement of catalytic activity or binding in a particular assay. Drawing more diffusion samples can explore candidate structures, but those samples are not automatically a thermodynamic ensemble.
I wrote a guide to those choices, including what to record before comparing models or interpreting their scores: https://rewire.it/blog/a-fasta-file-is-not-a-specification/
The useful evaluation question is which biological claim the output supports. What evidence would you require before carrying a model-selected structure into a downstream functional claim?