药物分子设计第九讲.pptVIP

蛋白质结构预测(一) Protein Structure Prediction (I) Protein Structure Prediction From Sequence to Native Structure Protein Structure Prediction Protein Structure Prediction Multiple Sequence Alignment Tools ClustalW Multiple sequence alignments reveal: conservation of individual residues conservation of regions differences within protein families Tools HMMer Profile For each position along the sequence, tabulate how often each type of amino acid occur (include ‘.’ for gap) The profile is always of size Nx21, no matter how many sequences are considered Protein Structure Prediction Secondary Structure Prediction Given a protein sequence a1a2…aN, secondary structure prediction aims at defining the state of each amino acid ai as being either H (helix), E (extended strand), or O (other) (Some methods have 4 states: H, E, T for turns, and O for other). The quality of secondary structure prediction is measured with a Qindex (Qhelix, Qstrand, Qcoil) or Q3. Q3 is the percent of residues that match “reality” (X-ray structure). Secondary Structure Prediction Secondary Structure Prediction Chou-Fasman Method Start by computing amino acids propensities to belong to a given type of secondary structure: Propensities 1 mean that the residue type i is likely to be found in the corresponding secondary structure type. Secondary Structure Prediction Chou-Fasman Method Secondary Structure Prediction Chou-Fasman Method Helix prediction 沿着蛋白质序列寻找?螺旋核，相邻的6个残基中如果有至少4个残基倾向于形成?螺旋，即有4个残基对应的P? 100，则认为是螺旋核。 然后从螺旋核向两端延伸，直至四肽片段P? 的平均值小于100为止。按上述方式找到的片段长度大于5，并且P? 的平均值大于P? 的平均值，那么这个片段的二级结构就被预测为?螺旋。此外，不容许Pro在螺旋内部出现，但可出现在C末端以及N端的前三位，这也用于终止螺旋的延伸。 Secondary Structure Prediction Chou-Fasman Method Strand Prediction 如果相邻6个残基中若有4个倾向于形成β折叠，即有4个残基对应的P? 100，则认为是折叠核。 折叠核向两端延伸直至4个残基P? 的平均值小于100为止。若延伸后片段的P? 的平均值大于105，并且P? 的平均值大于P? 的平均值，则该片段被预测为β折叠。 Secondary Structure Prediction Chou-Fasman Method Turn Prediction 转角的模型为四肽组合模型，要考虑每个位置上残基的组合概率，即特定残基在四肽模型中各个位置的概率。 在计算过程中，对于从第i个残基开始的连续4个残基的片段，将上述概率相