当前位置： SCI文献检索 > JOURNAL OF MOLECULAR BIOLOGY期刊下所有文献 > MPTherm-Pred: Analysis and Prediction of Thermal Stability Changes upon Mutations in Transmembrane Proteins.

MPTherm-Pred: Analysis and Prediction of Thermal Stability Changes upon Mutations in Transmembrane Proteins.

Abstract：

:The stability of membrane proteins differs from globular proteins due to the presence of nonpolar membrane-spanning regions. Using a dataset of 929 membrane protein mutations whose effects on thermal stability (ΔTm) were experimentally determined, we found that the average ΔTm due to 190 stabilizing and 232 destabilizing mutations occurring in membrane-spanning regions are 2.43 ± 3.1 and - 5.48 ± 5.5 °C, respectively. The ΔTm values for mutations occurring in solvent-exposed regions are 2.56 ± 2.82 and - 6.8 ± 7.2 °C. We have systematically analyzed the factors influencing the stability of mutants and observed that changes in hydrophobicity, number of contacts between Cα atoms and frequency of aliphatic residues are important determinants of the stability change induced by mutations occurring in membrane-spanning regions. We have developed structure- and sequence-based machine learning predictors of ΔTm due to mutations specifically for membrane proteins. They showed a correlation and mean absolute error (MAE) of 0.72 and 2.85 °C, respectively, between experimental and predicted ΔTm for mutations in membrane-spanning regions on 10-fold group-wise cross-validation. The average correlation and MAE for mutations in aqueous regions are 0.73 and 3.7 °C, respectively. These MAE values are about 50% lower than standard deviations from the mean ΔTm values. The reliability of the method was affirmed on a test set of mutations occurring in evolutionary independent protein sequences. The developed MPTherm-pred server for predicting thermal stability changes upon mutations in membrane proteins is available at https://web.iitm.ac.in/bioinfo2/mpthermpred/. Our results provide insights into factors influencing the stability of membrane proteins and can aid in designing mutants that are more resistant to thermal stress.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Kulandaisamy A,Zaucha J,Frishman D,Gromiha MM

doi

10.1016/j.jmb.2020.09.005

subject

Has Abstract

pub_date

2020-09-10 00:00:00

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(20)30538-6

pub_type

杂志文章,评审

在线工具

MPTherm-Pred: Analysis and Prediction of Thermal Stability Changes upon Mutations in Transmembrane Proteins.