Native protein sequences are close to optimal for their structures

TitleNative protein sequences are close to optimal for their structures
Publication TypeJournal Article
Year of Publication2000
AuthorsKuhlman, B., & Baker D.
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue19
Pagination10383-8
Date Published2000 Sep 12
ISSN0027-8424
KeywordsAmino Acid Sequence, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Primary Publication, Protein Conformation, Proteins, Sequence Homology, Amino Acid
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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
AttachmentSize
kuhlman00A.pdf142.94 KB