PremPDI estimates and interprets the effects of missense mutations on protein-DNA interactions.
Protein-DNA interactions play important roles in regulations of many vital cellular processes, including transcription, translation, DNA replication and recombination. Sequence variants occurring in these DNA binding proteins that alter protein-DNA interactions may cause significant perturbations or...
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2018-12-01
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Online Access: | https://doi.org/10.1371/journal.pcbi.1006615 |
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doaj-e9346388a9444f08977e3fdf2caffdd72021-04-21T15:12:22ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582018-12-011412e100661510.1371/journal.pcbi.1006615PremPDI estimates and interprets the effects of missense mutations on protein-DNA interactions.Ning ZhangYuting ChenFeiyang ZhaoQing YangFranco L SimonettiMinghui LiProtein-DNA interactions play important roles in regulations of many vital cellular processes, including transcription, translation, DNA replication and recombination. Sequence variants occurring in these DNA binding proteins that alter protein-DNA interactions may cause significant perturbations or complete abolishment of function, potentially leading to diseases. Developing a mechanistic understanding of impacts of variants on protein-DNA interactions becomes a persistent need. To address this need we introduce a new computational method PremPDI that predicts the effect of single missense mutation in the protein on the protein-DNA interaction and calculates the quantitative binding affinity change. The PremPDI method is based on molecular mechanics force fields and fast side-chain optimization algorithms with parameters optimized on experimental sets of 219 mutations from 49 protein-DNA complexes. PremPDI yields a very good agreement between predicted and experimental values with Pearson correlation coefficient of 0.71 and root-mean-square error of 0.86 kcal mol-1. The PremPDI server could map mutations on a structural protein-DNA complex, calculate the associated changes in binding affinity, determine the deleterious effect of a mutation, and produce a mutant structural model for download. PremPDI can be applied to many tasks, such as determination of potential damaging mutations in cancer and other diseases. PremPDI is available at http://lilab.jysw.suda.edu.cn/research/PremPDI/.https://doi.org/10.1371/journal.pcbi.1006615 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ning Zhang Yuting Chen Feiyang Zhao Qing Yang Franco L Simonetti Minghui Li |
spellingShingle |
Ning Zhang Yuting Chen Feiyang Zhao Qing Yang Franco L Simonetti Minghui Li PremPDI estimates and interprets the effects of missense mutations on protein-DNA interactions. PLoS Computational Biology |
author_facet |
Ning Zhang Yuting Chen Feiyang Zhao Qing Yang Franco L Simonetti Minghui Li |
author_sort |
Ning Zhang |
title |
PremPDI estimates and interprets the effects of missense mutations on protein-DNA interactions. |
title_short |
PremPDI estimates and interprets the effects of missense mutations on protein-DNA interactions. |
title_full |
PremPDI estimates and interprets the effects of missense mutations on protein-DNA interactions. |
title_fullStr |
PremPDI estimates and interprets the effects of missense mutations on protein-DNA interactions. |
title_full_unstemmed |
PremPDI estimates and interprets the effects of missense mutations on protein-DNA interactions. |
title_sort |
prempdi estimates and interprets the effects of missense mutations on protein-dna interactions. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Computational Biology |
issn |
1553-734X 1553-7358 |
publishDate |
2018-12-01 |
description |
Protein-DNA interactions play important roles in regulations of many vital cellular processes, including transcription, translation, DNA replication and recombination. Sequence variants occurring in these DNA binding proteins that alter protein-DNA interactions may cause significant perturbations or complete abolishment of function, potentially leading to diseases. Developing a mechanistic understanding of impacts of variants on protein-DNA interactions becomes a persistent need. To address this need we introduce a new computational method PremPDI that predicts the effect of single missense mutation in the protein on the protein-DNA interaction and calculates the quantitative binding affinity change. The PremPDI method is based on molecular mechanics force fields and fast side-chain optimization algorithms with parameters optimized on experimental sets of 219 mutations from 49 protein-DNA complexes. PremPDI yields a very good agreement between predicted and experimental values with Pearson correlation coefficient of 0.71 and root-mean-square error of 0.86 kcal mol-1. The PremPDI server could map mutations on a structural protein-DNA complex, calculate the associated changes in binding affinity, determine the deleterious effect of a mutation, and produce a mutant structural model for download. PremPDI can be applied to many tasks, such as determination of potential damaging mutations in cancer and other diseases. PremPDI is available at http://lilab.jysw.suda.edu.cn/research/PremPDI/. |
url |
https://doi.org/10.1371/journal.pcbi.1006615 |
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