dorsal/arxiv
View SchemaPositive and negative design in stability and thermal adaptation of natural proteins
| Authors | Igor N. Berezovsky, Konstantin B. Zeldovich, Eugene I. Shakhnovich |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0607003 |
| URL | https://arxiv.org/abs/q-bio/0607003 |
| DOI | 10.1371/journal.pcbi.0030052 |
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, i.e. 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 hydrophobicity scale trend is due to positive (to stabilize the native state) and negative (to destabilize misfolded states) components of protein design. Negative design strengthens specific repulsive nonnative interactions that appear in misfolded structures. A pressure to preserve specific repulsive interactions in non-native conformations may result in correlated mutations between amino acids which are far apart in the native state but may be in contact in misfolded conformations. Such correlated mutations are indeed found in TIM barrel and other proteins.
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"abstract": "The aim of this work is to elucidate how physical principles of protein\ndesign are reflected in natural sequences that evolved in response to the\nthermal conditions of the environment. Using an exactly solvable lattice model,\nwe design sequences with selected thermal properties. Compositional analysis of\ndesigned model sequences and natural proteomes reveals a specific trend in\namino acid compositions in response to the requirement of stability at elevated\nenvironmental temperature, i.e. the increase of fractions of hydrophobic and\ncharged amino acid residues at the expense of polar ones. We show that this\nfrom both ends of hydrophobicity scale trend is due to positive (to stabilize\nthe native state) and negative (to destabilize misfolded states) components of\nprotein design. Negative design strengthens specific repulsive nonnative\ninteractions that appear in misfolded structures. A pressure to preserve\nspecific repulsive interactions in non-native conformations may result in\ncorrelated mutations between amino acids which are far apart in the native\nstate but may be in contact in misfolded conformations. Such correlated\nmutations are indeed found in TIM barrel and other proteins.",
"arxiv_id": "q-bio/0607003",
"authors": [
"Igor N. Berezovsky",
"Konstantin B. Zeldovich",
"Eugene I. Shakhnovich"
],
"categories": [
"q-bio.BM"
],
"doi": "10.1371/journal.pcbi.0030052",
"title": "Positive and negative design in stability and thermal adaptation of natural proteins",
"url": "https://arxiv.org/abs/q-bio/0607003"
},
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