title: Natural protein sequences are more intrinsically disordered than random sequences.
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.
authors.affiliation: Shandong Provincial Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, 253023, China.
authors.forename: Jia-Feng
authors.initials: JF
authors.lastname: Yu
authors.affiliation: Shandong Provincial Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, 253023, China.|College of Physics and Electronic Information, Dezhou University, Dezhou, 253023, China.
authors.forename: Zanxia
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Institute for Glycomics and School of Information and Communication Technology, Griffith University, Parklands Dr, Southport, QLD, 4222, Australia.
authors.forename: Yuedong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Physics and Electronic Information, Dezhou University, Dezhou, 253023, China.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, 253023, China.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Su
authors.affiliation: Shandong Provincial Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, 253023, China.
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, 253023, China.|College of Physics and Electronic Information, Dezhou University, Dezhou, 253023, China.
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, 253023, China. yaoqi.zhou@griffith.edu.au.|Institute for Glycomics and School of Information and Communication Technology, Griffith University, Parklands Dr, Southport, QLD, 4222, Australia. yaoqi.zhou@griffith.edu.au.
authors.forename: Yaoqi
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D019295:Computational Biology; D030562:Databases, Protein; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D066329:Protein Aggregates; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D020539:Sequence Analysis, Protein
chemical_list: D000596:Amino Acids; D064267:Intrinsically Disordered Proteins; D066329:Protein Aggregates; D011506:Proteins
keywords: Molecular dynamics simulation; Molten globule; Protein intrinsic disorder; Random sequence; Secondary structure