{"doi":"10.1093/bioinformatics/bty975","title":"A structural homology approach for computational protein design with flexible backbone","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Motivation</jats:title>\n                  <jats:p>Structure-based Computational Protein design (CPD) plays a critical role in advancing the field of protein engineering. Using an all-atom energy function, CPD tries to identify amino acid sequences that fold into a target structure and ultimately perform a desired function. Energy functions remain however imperfect and injecting relevant information from known structures in the design process should lead to improved designs.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>We introduce Shades, a data-driven CPD method that exploits local structural environments in known protein structures together with energy to guide sequence design, while sampling side-chain and backbone conformations to accommodate mutations. Shades (Structural Homology Algorithm for protein DESign), is based on customized libraries of non-contiguous in-contact amino acid residue motifs. We have tested Shades on a public benchmark of 40 proteins selected from different protein families. When excluding homologous proteins, Shades achieved a protein sequence recovery of 30% and a protein sequence similarity of 46% on average, compared with the PFAM protein family of the target protein. When homologous structures were added, the wild-type sequence recovery rate achieved 93%.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation</jats:title>\n                  <jats:p>Shades source code is available at https://bitbucket.org/satsumaimo/shades as a patch for Rosetta 3.8 with a curated protein structure database and ITEM library creation software.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information</jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.</jats:p>\n               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