Manipulation of protein backbones is important in understanding and designing binding sites. We are interested in characterizing the geometric and analytic properties of such protein backbone manipulations, and have developed geometric tools to analytically calculate the positions and derivatives of intermediate atoms under small modifications in ideal geometry.

We have started to incorporate local protein backbone motions into the protein design process. A simple geometric motion that captures local plasticity has been developed. We are using this to generate side-chain rotamer libraries in situ to generate the sequence diversity permitted by this plastic deformation. These (very large) libraries are being used in new design calculations, and experimentally tested. A TNT receptor designed with a modified backbone shows, in silico, better characteristics than a previous design with a rigid backbone.