Role of solvent accessibility for aggregation-prone patches in protein folding

15Citations
Citations of this article
33Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The arrangement of amino acids in a protein sequence encodes its native folding. However, the same arrangement in aggregation-prone regions may cause misfolding as a result of local environmental stress. Under normal physiological conditions, such regions congregate in the protein’s interior to avoid aggregation and attain the native fold. We have used solvent accessibility of aggregation patches (SAAPp) to determine the packing of aggregation-prone residues. Our results showed that SAAPp has low values for native crystal structures, consistent with protein folding as a mechanism to minimize the solvent accessibility of aggregation-prone residues. SAAPp also shows an average correlation of 0.76 with the global distance test (GDT) score on CASP12 template-based protein models. Using SAAPp scores and five structural features, a random forest machine learning quality assessment tool, SAAP-QA, showed 2.32 average GDT loss between best model predicted and actual best based on GDT score on independent CASP test data, with the ability to discriminate native-like folds having an AUC of 0.94. Overall, the Pearson correlation coefficient (PCC) between true and predicted GDT scores on independent CASP data was 0.86 while on the external CAMEO dataset, comprising high quality protein structures, PCC and average GDT loss were 0.71 and 4.46 respectively. SAAP-QA can be used to detect the quality of models and iteratively improve them to native or near-native structures.

References Powered by Scopus

Random forests

94709Citations
N/AReaders
Get full text

The Protein Data Bank

32036Citations
N/AReaders
Get full text

Principles that govern the folding of protein chains

5662Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Structure-based machine-guided mapping of amyloid sequence space reveals uncharted sequence clusters with higher solubilities

59Citations
N/AReaders
Get full text

Protein aggregation: in silico algorithms and applications

47Citations
N/AReaders
Get full text

Explicit-solvent molecular dynamics simulations revealed conformational regain and aggregation inhibition of I113T SOD1 by Himalayan bioactive molecules

23Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Mishra, A., Ranganathan, S., Jayaram, B., & Sattar, A. (2018). Role of solvent accessibility for aggregation-prone patches in protein folding. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-31289-6

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 9

50%

Researcher 7

39%

Professor / Associate Prof. 2

11%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 9

56%

Physics and Astronomy 3

19%

Agricultural and Biological Sciences 3

19%

Pharmacology, Toxicology and Pharmaceut... 1

6%

Save time finding and organizing research with Mendeley

Sign up for free