Proteins of well-defined structures can be designed without backbone readjustment by a statistical model

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• 作者：Xiaoqun Zhou^a ; Peng Xiong^a ; Meng Wang^a ; Rongsheng Ma^a ; Jiahai Zhang^a ; Quan Chen^a ; ^{chenquan@ustc.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Haiyan Liu^a ; ^b ; ^c ; ^d ; ^{hyliu@ustc.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ABACUS ; acronym for A Backbone based Amino aCid Usage Survey ; CPD ; computational protein design ; NMR ; nuclear magnetic resonance ; HSQC ; heteronuclear single quantum coherence spectra ; NOE ; nuclear Overhauser enhancement ; RDC ; backbone residual dipolar coupling ; SAI ; solvent accessibility indices ; RMSD ; the root-mean-square-deviation ; vdW ; van der Waals
• 刊名：Journal of Structural Biology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：196
• 期：3
• 页码：350-357
• 全文大小：1969 K

文摘

We report that using mainly a statistical energy model, protein sequence design for designable backbones can be carried out with high confidence without considering backbone relaxation. A recently-developed statistical energy function for backbone-based protein sequence design has been rationally revised to improve its accuracy. As a demonstrative example, this revised model is applied to design a de novo protein for a target backbone for which the previous model had relied on after-design directed evolution to produce a well-folded protein. The actual backbone structure of the newly designed protein agrees excellently with the corresponding target. Besides presenting a new protein design protocol with experimentally verifications on different backbone types, our study implies that with an energy model of an appropriate resolution, proteins of well-defined structures instead of molten globules can be designed without the explicit consideration of backbone variations due to side chain changes, even if the side chain changes correspond to complete sequence redesigns.