Positive and negative design in stability and thermal adaptation of natural proteins.

ABSTRACT: The aim of this work is to elucidate how physical principles of protein design are reflected in natural sequences that evolved in response to the thermal conditions of the environment. Using an exactly solvable lattice model, we design sequences with selected thermal properties. Compositional analysis of designed model sequences and natural proteomes reveals a specific trend in amino acid compositions in response to the requirement of stability at elevated environmental temperature: the increase of fractions of hydrophobic and charged amino acid residues at the expense of polar ones. We show that this "from both ends of the hydrophobicity scale" trend is due to positive (to stabilize the native state) and negative (to destabilize misfolded states) components of protein design. Negative des

SUBMITTER: Berezovsky IN 

PROVIDER: S-EPMC1829478 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature