Codon selection reduces GC content bias in nucleic acids encoding for intrinsically disordered proteins

Background: Intrinsically disordered proteins lack a well-defined three-dimensional structure under physiological conditions. They have performed multiple functions in life activities and are closely related to many human diseases. The identification of the disordered region of intrinsically disordered proteins is important to protein functions annotation. Objective : Accurately identify the disordered regions in intrinsically disordered proteins. Method: In this article, we constructed a multi-feature fusion model based on support vector machine to predict disordered regions of intrinsically disordered proteins from the Disport database. We extracted codons usage frequencies, GC content, protein secondary structure components, hydrophilic-hydrophobic amino acidscomponents, and chemical shifts as features to predict the disordered regionsofintrinsically disordered proteins. Results : The best accuracy is 82.098% by using codons frequenciesin single feature prediction.In order to improve the performance, we fused these features and obtained the best result of 83.173%in combining codons frequencies with chemical shifts as the feature. Conclusion : The results show that our model has achieved a good prediction result in predicting disordered regions of intrinsically disordered proteins. Moreover, the performances of our modelare better than those of existing methods.

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Intrinsically disordered proteins share a common molecular mechanism in membranes damages: Lipid-chaperone hypothesis

10.1021/scimeetings.0c02079 ◽

2020 ◽

Author(s):

Carmelo La Rosa

Keyword(s):

Molecular Mechanism ◽

Intrinsically Disordered Proteins ◽

Disordered Proteins ◽

Intrinsically Disordered

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Intrinsically Disordered Proteins

10.1016/s0076-6879(18)x0012-3 ◽

2018 ◽

Keyword(s):

Intrinsically Disordered Proteins ◽

Disordered Proteins ◽

Intrinsically Disordered

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Sequence Specificity Despite Intrinsic Disorder: How a Disease-Associated Val/Met Polymorphism Shifts Tertiary Interactions in a Long Disordered Protein

10.26434/chemrxiv.8135777.v1 ◽

2019 ◽

Author(s):

Ruchi Lohia ◽

Reza Salari ◽

Grace Brannigan

Keyword(s):

Secondary Structure ◽

Electrostatic Interactions ◽

Intrinsically Disordered Proteins ◽

Disordered Proteins ◽

Sequence Specificity ◽

Intrinsically Disordered ◽

Specific Effects ◽

Heterogeneous Polymer ◽

Non Local ◽

Dynamics Simulations

<div>The role of electrostatic interactions and mutations that change charge states in intrinsically disordered proteins (IDPs) is well-established, but many disease-associated mutations in IDPs are charge-neutral. The Val66Met single nucleotide polymorphism (SNP) encodes a hydrophobic-to-hydrophobic mutation at the midpoint of the prodomain of precursor brain-derived neurotrophic factor (BDNF), one of the earliest SNPs to be associated with neuropsychiatric disorders, for which the underlying molecular mechanism is unknown. Here we report on over 250 μs of fully-atomistic, explicit solvent, temperature replica exchange molecular dynamics simulations of the 91 residue BDNF prodomain, for both the V66 and M66 sequence.</div><div>The simulations were able to correctly reproduce the location of both local and non-local secondary changes due to the Val66Met mutation when compared with NMR spectroscopy. We find that the local structure change is mediated via entropic and sequence specific effects. We show that the highly disordered prodomain can be meaningfully divided into domains based on sequence alone. Monte Carlo simulations of a self-excluding heterogeneous polymer, with monomers representing each domain, suggest the sequence would be effectively segmented by the long, highly disordered polyampholyte near the sequence midpoint. This is qualitatively consistent with observed interdomain contacts within the BDNF prodomain, although contacts between the two segments are enriched relative to the self-excluding polymer. The Val66Met mutation increases interactions across the boundary between the two segments, due in part to a specific Met-Met interaction with a Methionine in the other segment. This effect propagates to cause the non-local change in secondary structure around the second methionine, previously observed in NMR. The effect is not mediated simply via changes in inter-domain contacts but is also dependent on secondary structure formation around residue 66, indicating a mechanism for secondary structure coupling in disordered proteins. </div>

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