Send to

Choose Destination
J Struct Biol. 2014 Feb;185(2):136-46. doi: 10.1016/j.jsb.2013.03.012. Epub 2013 Apr 1.

An accurate binding interaction model in de novo computational protein design of interactions: if you build it, they will bind.

Author information

Rosetta Design Group LLC, Fairfax, VA 22030, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA. Electronic address:
Rosetta Design Group LLC, Fairfax, VA 22030, USA. Electronic address:


Computational protein design efforts aim to create novel proteins and functions in an automated manner and, in the process, these efforts shed light on the factors shaping natural proteins. The focus of these efforts has progressed from the interior of proteins to their surface and the design of functions, such as binding or catalysis. Here we examine progress in the development of robust methods for the computational design of non-natural interactions between proteins and molecular targets such as other proteins or small molecules. This problem is referred to as the de novo computational design of interactions. Recent successful efforts in de novo enzyme design and the de novo design of protein-protein interactions open a path towards solving this problem. We examine the common themes in these efforts, and review recent studies aimed at understanding the nature of successes and failures in the de novo computational design of interactions. While several approaches culminated in success, the use of a well-defined structural model for a specific binding interaction in particular has emerged as a key strategy for a successful design, and is therefore reviewed with special consideration.


Binding interaction model; Computational design; De novo design; Enzyme design; Protein–protein interaction design; ROSETTA

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center