Structurally constrained protein evolution: results from a lattice simulation |
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Authors: | U Bastolla M Vendruscolo HE Roman |
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Institution: | (1) FU Berlin, Inst. für Kristallographie, Takustrasse 6, 14195 Berlin, Germany, DE;(2) Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel, IL;(3) INFN, Sezione di Milano, Università di Milano, Via Celoria 16, 20133 Milano, Italy, IT |
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Abstract: | We simulate the evolution of a protein-like sequence subject to point mutations, imposing conservation of the ground state,
thermodynamic stability and fast folding. Our model is aimed at describing neutral evolution of natural proteins. We use a
cubic lattice model of the protein structure and test the neutrality conditions by extensive Monte Carlo simulations. We observe
that sequence space is traversed by neutral networks, i.e. sets of sequences with the same fold connected by point mutations. Typical pairs of sequences on a neutral network are nearly
as different as randomly chosen sequences. The fraction of neutral neighbors has strong sequence to sequence variations, which
influence the rate of neutral evolution. In this paper we study the thermodynamic stability of different protein sequences.
We relate the high variability of the fraction of neutral mutations to the complex energy landscape within a neutral network,
arguing that valleys in this landscape are associated to high values of the neutral mutation rate. We find that when a point
mutation produces a sequence with a new ground state, this is likely to have a low stability. Thus we tentatively conjecture
that neutral networks of different structures are typically well separated in sequence space. This result indicates that changing
significantly a protein structure through a biologically acceptable chain of point mutations is a rare, although possible,
event.
Received 8 July 1999 |
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Keywords: | PACS 87 15 Aa Theory and modeling computer simulation - 87 23 Kg Dynamics of evolution |
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