Toward complete rational control over protein structure and function through computational design. (February 2021) - Adolf-Bryfogle, Jared
Highlights: The grand challenge of computational protein design is the generalized ability to confer arbitrary functions and properties. Protein shape, function and solution behavior are individually designable. Protein dynamics are critical to predicting and designing function and this remains an active research frontier. Informatic advancements have enlarged the set of designable proteins. Abstract : The grand challenge of protein design is a general method for producing a polypeptide with arbitrary functionality, conformation, and biochemical properties. To that end, a wide variety of methods have been developed for the improvement of native proteins, the design of ideal proteins de novo, and the redesign of suboptimal proteins with better-performing substructures. These methods employ informatic comparisons of function-structure-sequence relationships as well as knowledge-based evaluation of protein properties to narrow the immense protein sequence search space down to an enumerable and often manually evaluable set of structures that meet specified criteria. While arbitrary manipulation of protein–protein interfaces and molecular catalysis remains an unsolved problem, and no protein shape or behavior manipulation algorithm is universally applicable, the promising results thus far are a strong indicator that a general approach to the arbitrary manipulation of polypeptides is within reach.