title: Energy functions in de novo protein design: current challenges and future prospects.
abstract: In the past decade, a concerted effort to successfully capture specific tertiary packing interactions produced specific three-dimensional structures for many de novo designed proteins that are validated by nuclear magnetic resonance and/or X-ray crystallographic techniques. However, the success rate of computational design remains low. In this review, we provide an overview of experimentally validated, de novo designed proteins and compare four available programs, RosettaDesign, EGAD, Liang-Grishin, and RosettaDesign-SR, by assessing designed sequences computationally. Computational assessment includes the recovery of native sequences, the calculation of sizes of hydrophobic patches and total solvent-accessible surface area, and the prediction of structural properties such as intrinsic disorder, secondary structures, and three-dimensional structures. This computational assessment, together with a recent community-wide experiment in assessing scoring functions for interface design, suggests that the next-generation protein-design scoring function will come from the right balance of complementary interaction terms. Such balance may be found when more negative experimental data become available as part of a training set.
authors: School of Informatics, Indiana University-Purdue University, Indianapolis, Indiana 46202, USA.
authors: Zhixiu
authors: Z
authors: Li
authors: Yuedong
authors: Y
authors: Yang
authors: Jian
authors: J
authors: Zhan
authors: Liang
authors: L
authors: Dai
authors: Yaoqi
authors: Y
authors: Zhou
mesh_terms: D001419:Bacteria / Q000737:chemistry / Q000378:metabolism; D017076:Computer-Aided Design; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013816:Thermodynamics
chemical_list: D011506:Proteins