title: An Evolution-Based Approach to De Novo Protein Design.
abstract: EvoDesign is a computational algorithm that allows the rapid creation of new protein sequences that are compatible with specific protein structures. As such, it can be used to optimize protein stability, to resculpt the protein surface to eliminate undesired protein-protein interactions, and to optimize protein-protein binding. A major distinguishing feature of EvoDesign in comparison to other protein design programs is the use of evolutionary information in the design process to guide the sequence search toward native-like sequences known to adopt structurally similar folds as the target. The observed frequencies of amino acids in specific positions in the structure in the form of structural profiles collected from proteins with similar folds and complexes with similar interfaces can implicitly capture many subtle effects that are essential for correct folding and protein-binding interactions. As a result of the inclusion of evolutionary information, the sequences designed by EvoDesign have native-like folding and binding properties not seen by other physics-based design methods. In this chapter, we describe how EvoDesign can be used to redesign proteins with a focus on the computational and experimental procedures that can be used to validate the designs.
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI, 48109-2218, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Brender
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI, 48109-2218, USA.
authors.forename: David
authors.initials: D
authors.lastname: Shultis
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI, 48109-2218, USA.
authors.forename: Naureen Aslam
authors.initials: NA
authors.lastname: Khattak
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI, 48109-2218, USA. zhng@umich.edu.|Department of Biological Chemistry, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI, 48109-2218, USA. zhng@umich.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D003198:Computer Simulation; D030562:Databases, Protein; D019143:Evolution, Molecular; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D015203:Reproducibility of Results; D012984:Software; D012995:Solubility; D064878:Web Browser
chemical_list: D011506:Proteins
keywords: Circular dichroism; Evolutionary profile; Experimental protein validation; Nuclear magnetic resonance; Protein design; Protein structure modeling; Recombinant expression