Computational de novo peptide and protein design: Rigid templates versus flexible templates

Both rigid and flexible backbone design templates have been used in the numerous computational de novo peptide and protein design efforts reported so far. In this review paper, we use the type of templates (i.e., rigid or flexible) as a criterion to classify and review examples of successes in de novo protein design. For both cases of rigid and flexible templates, we briefly outline the different search methods for exploring the sequence space and quote some notable success examples for each search method. In particular, we divide the case of flexible templates into three subcategories, according to their approaches for incorporating backbone flexibility: (i) discrete rotamers on multiple backbones with fixed backbone assumption for each, (ii) discrete rotamers on a continuum backbone through algebraic parametrization, and (iii) continuum backbone template with continuous ranges of backbone angles.