Natural protein sequences are more intrinsically disordered than random sequences

Cellular and Molecular Life Sciences : CMLS
Jia-Feng YuYaoqi Zhou

Abstract

Most natural protein sequences have resulted from millions or even billions of years of evolution. How they differ from random sequences is not fully understood. Previous computational and experimental studies of random proteins generated from noncoding regions yielded inclusive results due to species-dependent codon biases and GC contents. Here, we approach this problem by investigating 10,000 sequences randomized at the amino acid level. Using well-established predictors for protein intrinsic disorder, we found that natural sequences have more long disordered regions than random sequences, even when random and natural sequences have the same overall composition of amino acid residues. We also showed that random sequences are as structured as natural sequences according to contents and length distributions of predicted secondary structure, although the structures from random sequences may be in a molten globular-like state, according to molecular dynamics simulations. The bias of natural sequences toward more intrinsic disorder suggests that natural sequences are created and evolved to avoid protein aggregation and increase functional diversity.

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Citations

Nov 15, 2017·Scientific Reports·Vyacheslav TretyachenkoKlára Hlouchová
Aug 8, 2017·Molecular BioSystems·Sanghita Banerjee, Sandip Chakraborty
Jun 15, 2018·Genome Biology and Evolution·Jordi MorataJosep M Casacuberta
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Dec 22, 2020·Genomics, Proteomics & Bioinformatics·Arup Panda, Tamir Tuller
Mar 26, 2021·Genes & Genetic Systems·Morteza M SaberNaruya Saitou

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Methods Mentioned

BETA
NMR
X-ray

Software Mentioned

Prnd
Preq
IUpred
SPARKS
SPIDER2
GROMACS
MD
CD
SPIDER
HIT

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