Homology Modeling: How it works --KSPkEVTMKGDILTLLNSTNKDww KID 肝细胞生长因子 Ibym RKVRivQINEIFOVETDOFTOLDADIRVGSEVEIVDRDChr 1白喉毒素 o Find template(模板) o Align target sequence with template Template: Ishg Framework o Generate mode/ add loops add sidechains o Refine model Model: 1brm
Homology Modeling: How it works o Find template（模板） o Align target sequence with template o Generate model: - add loops - add sidechains o Refine model 肝细胞生长因子 白喉毒素
选择合适的模板是关键步骤 Selecting the best template is crucial The best template may not be the one with the highest id( best p-value .) Template 1: 93% id, 3.5 A resolution Template 2 90% id, 1.5 A resolution e Safe homology 30 Twlight zone Number of aligned residues
选择合适的模板是关键步骤
Homology Modeling: How It works well? Comparable to medium 二磷 resolution NMR. low resolution crystallography 酸核 苷激 Docking of small ligands 酶 human nucleoside 60 diphosphate kinase Molecular replacement in 视黄 Sali, A& Kuriyan, J. Trends crystallography. 酸结 Biochem. ScL. 22, M20-M24 (1999) Supporting site-directed 合蛋 5 mouse cellular retinoic 子30 acid binding protein I Refining NMR structures. 嗜酸 Finding binding/active sites 性粒 g 细胞 Annotating function by 神经 fold assignment 0 毒素 human eosinophil neurotoxin
Homology Modeling: How It works well? Sali, A. & Kuriyan, J. Trends Biochem. Sci. 22, M20–M24 (1999) 二磷 酸核 苷激 酶 视黄 酸结 合蛋 白I 嗜酸 性粒 细胞 神经 毒素
Refinement(结构修正)? CASP5赛事评委对同源建模方法的评论: We are forced to draw the disappointing conclusion that, similarly to what observed in previous editions of the experiment, no model resulted to be closer to the target structure than the template to any significant extent 同源建模的结果通常不可轻易修正, 修正的后果往往背离其真实结构!
Refinement (结构修正)? CASP5 赛事评委对同源建模方法的评论: “We are forced to draw the disappointing conclusion that, similarly to what observed in previous editions of the experiment, no model resulted to be closer to the target structure than the template to any significant extent.” 同源建模的结果通常不可轻易修正， 修正的后果往往背离其真实结构！
The casP experiment CASP= Critica/ Assessment of Structure Prediction Started in 1994. based on an idea from john moult (Moult, Pederson, Judson, Fidelis, Proteins, 23: 2-5 (1995 First run in 1994, now runs regularly every second year (CASP10 was held last April http:/predictioncenter.orgy
The CASP experiment • CASP= Critical Assessment of Structure Prediction • Started in 1994, based on an idea from John Moult (Moult, Pederson, Judson, Fidelis, Proteins, 23:2-5 (1995)) • First run in 1994; now runs regularly every second year (CASP10 was held last April) • http://predictioncenter.org/