TITLE

Emergence of stable and fast folding protein structures

AUTHOR(S)
Thirumalai, D.; Klimov, D. K.
PUB. DATE
February 2000
SOURCE
AIP Conference Proceedings;2000, Vol. 501 Issue 1, p95
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The number of protein structures is far less than the number of sequences. By imposing simple generic features of proteins (low energy and compaction) on all possible sequences we show that the structure space is sparse compared to the sequence space. Even though the sequence space grows exponentially with N (the number of amino acid residues) we conjecture that the number of low energy compact structures only scales as lnN. This implies that many sequences must map onto countable number of basins in the structure space. The number of sequences for which a given fold emerges as a native structure is further reduced by the dual requirements of stability and kinetic accessibility. The factor that determines the dual requirement is related to the sequence dependent temperatures, T[sub θ] (collapse transition temperature) and T[sub F] (folding transition temperature). Sequences, for which σ=(T[sub θ]-T[sub F])/T[sub θ] is small, typically fold fast by generically collapsing to the native-like structures and then rapidly assembling to the native state. Such sequences satisfy the dual requirements over a wide temperature range. We also suggest that the functional requirement may further reduce the number of sequences that are biologically competent. The scheme developed here for thinning of the sequence space that leads to foldable structures arises naturally using simple physical characteristics of proteins. The reduction in sequence space leading to the emergence of foldable structures is demonstrated using lattice models of proteins. © 2000 American Institute of Physics.
ACCESSION #
6028282

 

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