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