Native protein sequences are close to optimal for their structures.

ABSTRACT: How large is the volume of sequence space that is compatible with a given protein structure? Starting from random sequences, low free energy sequences were generated for 108 protein backbone structures by using a Monte Carlo optimization procedure and a free energy function based primarily on Lennard-Jones packing interactions and the Lazaridis-Karplus implicit solvation model. Remarkably, in the designed sequences 51% of the core residues and 27% of all residues were identical to the amino acids in the corresponding positions in the native sequences. The lowest free energy sequences obtained for ensembles of native-like backbone structures were also similar to the native sequence. Furthermore, both the individual residue frequencies and the covariances between pairs of positions observed

SUBMITTER: Kuhlman B 

PROVIDER: S-EPMC27033 | biostudies-literature | 2000 Sep

REPOSITORIES: biostudies-literature