Native protein sequences are close to optimal for their structures.

@article{citeulike:613989, 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 in the very large SH3 domain family were recapitulated in core sequences designed for SH3 domain structures. Taken together, these results suggest that the volume of sequence space optimal for a protein structure is surprisingly restricted to a region around the native sequence.}, address = {Department of Biochemistry and Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA 98195, USA.}, author = {Kuhlman, B. and Baker, D. }, citeulike-article-id = {613989}, doi = {http://dx.doi.org/10.1073/pnas.97.19.10383}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {bioinformatics, protein\_structure, proteinstability}, month = {September}, number = {19}, pages = {10383--10388}, posted-at = {2008-03-03 10:41:11}, priority = {2}, title = {Native protein sequences are close to optimal for their structures.}, url = {http://dx.doi.org/10.1073/pnas.97.19.10383}, volume = {97}, year = {2000} }

TY - JOUR ID - citeulike:613989 L3 - citeulike-article-id:613989 TI - Native protein sequences are close to optimal for their structures. JF - Proc Natl Acad Sci U S A VL - 97 IS - 19 SP - 10383 EP - 10388 AD - Department of Biochemistry and Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA 98195, USA. SN - 0027-8424 N2 - 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 in the very large SH3 domain family were recapitulated in core sequences designed for SH3 domain structures. Taken together, these results suggest that the volume of sequence space optimal for a protein structure is surprisingly restricted to a region around the native sequence. KW - bioinformatics KW - protein_structure KW - proteinstability AU - Kuhlman, B AU - Baker, D PY - 2000/09/12/ UR - http://dx.doi.org/10.1073/pnas.97.19.10383 ER -