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Modeling evolutionary landscapes: mutational stability, topology, and superfunnels in sequence space
1Theoretical Bioinformatics Group, German Cancer Research Centre Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Summary
Protein evolution favors sequences with maximum mutational stability. These "prototype sequences" are central to neutral nets, enhancing evolutionary populations and thermodynamic stability.
Area of Science:
- Evolutionary biology
- Biophysics
- Computational biology
Background:
- Understanding protein evolution requires studying random mutations under neutral conditions.
- Neutral nets connect genotypes with the same phenotype via single-point mutations.
Purpose of the Study:
- To investigate evolutionary trajectories on neutral nets.
- To analyze the relationship between sequence, structure, and stability.
Main Methods:
- Utilized simple exact lattice models for sequence-conformation mapping.
- Determined densities of states via exhaustive conformational enumeration.
- Compared two distinct interaction schemes for robustness.
Main Results:
- Sequences in neutral nets often center around a 'prototype sequence' with maximal mutational stability.
- Prototype sequences tolerate the most neutral mutations.
- Native thermodynamic stability generally increases towards the prototype sequence, forming funnel-like structures in sequence space.
Conclusions:
- Neutral net topology drives higher evolutionary populations at prototype sequences.
- These findings unify perspectives on protein sequence design, native stability, and mutational stability.
- Principles are generalizable to other fitness measures with smooth variation.