title: Proteins of well-defined structures can be designed without backbone readjustment by a statistical model.
abstract: 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.
authors: School of Life Sciences, China.
authors: Xiaoqun
authors: X
authors: Zhou
authors: School of Life Sciences, China.
authors: Peng
authors: P
authors: Xiong
authors: School of Life Sciences, China.
authors: Meng
authors: M
authors: Wang
authors: School of Life Sciences, China.
authors: Rongsheng
authors: R
authors: Ma
authors: School of Life Sciences, China.
authors: Jiahai
authors: J
authors: Zhang
authors: School of Life Sciences, China. Electronic address: chenquan@ustc.edu.cn.
authors: Quan
authors: Q
authors: Chen
authors: School of Life Sciences, China; Hefei National Laboratory for Physical Sciences at the Microscales, China; Collaborative Innovation Center of Chemistry for Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China. Electronic address: hyliu@ustc.edu.cn.
authors: Haiyan
authors: H
authors: Liu
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D003198:Computer Simulation; D008958:Models, Molecular; D015233:Models, Statistical; D011487:Protein Conformation; D015202:Protein Engineering; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics
chemical_list: D011506:Proteins
keywords: Computational protein design; Design accuracy; NMR structure determination; Protein foldability; Statistical energy function