PremPRI: Predicting the Effects of Missense Mutations on Protein–RNA Interactions
Abstract
:1. Introduction
2. Results and Discussion
2.1. Multiple Linear Regression Model of PremPRI
2.2. Performance on Three Types of Cross-Validation
2.3. Comparison with Other Methods
2.4. Online Webserver
2.4.1. Input
2.4.2. Output
3. Methods
3.1. Experimental Datasets Used for Training
3.2. Structural Optimization Protocol
3.3. The PremPRI Model
- is the difference of van der Waals interaction energies between mutant and wild type (). is the difference of van der Waals energies between a protein–RNA complex and each binding partner (Partner 1: protein; Partner 2: RNA), which is calculated using the ENERGY module of the CHARMM program [50].
- is the difference of van der Waals repulsive energies between mutant and wild type. Here, the van der Waals repulsive energy only counts the repulsion between the residue at the mutated site and the nucleotides.
- is the difference of electrostatic interaction energies between mutant and wild type ( = is the electrostatic interaction energy between the residue at the mutated site and its contact residues/nucleotides. If any side-chain atom/base of a residue/nucleotide is located within 10 Å from any side-chain atom of the mutated site, we defined it as a contact residue/nucleotide. The calculation is carried out using the ENERGY module of the CHARMM program.
- is the number of amino acids at the protein–RNA binding interface. If the solvent-accessible surface area of a residue in the protein is more than that in the complex, we define it as the interface residue. The SASA module of CHARMM is used to calculate the solvent-accessible surface area.
- is the ratio of protein length and its surface area. and SASA is the total number of residues and the solvent-accessible surface area of unbound protein, respectively. The structure of the unbound protein is extracted from the minimized wild-type complex structure.
- Closeness of the node of the mutated site in the residue interaction network. It is defined as:
- is the difference of solvent accessible surface areas between mutant and wild type ( = . is the solvent accessible surface area of the residue at the mutated site in the unbound protein that is extracted from the minimized complex structure.
- , and are the number of exposed residues in the coil conformation and all residues in the mutated protein chain, respectively. Secondary structure elements other than α-helices and β-strands are defined as coil, which are assigned by the DSSP program [53]. If the ratio of the solvent-accessible surface area of a residue in the complex and in solvent is more than 0.25 [54], we defined it as the exposed residue.
- is the difference of hydrophobicity scale between mutant and wild-type residue types. The hydrophobicity scale (OMH) for each type of amino acid was derived by considering the observed frequency of amino acid replacements among thousands of related structures, which was taken from the study of [55] directly.
- and = , = , and . , , and are the number of aromatic (F, W and Y), positively charged (K and R), negatively charged (D and E) and all amino acids in the mutated protein chain, respectively.
3.4. Statistical Analysis and Evaluation of Performance
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Method | R | RMSE | Slope |
---|---|---|---|
PremPRI | 0.72 | 0.76 | 1.00 |
PremPRI (CV1) | 0.68 | 0.80 | 0.94 |
PremPRI (CV2) | 0.68 | 0.80 | 0.95 |
PremPRI (CV3) | 0.61 | 0.87 | 0.89 |
Method | R | RMSE | AUC-ROC | AUC-PR | MCC |
---|---|---|---|---|---|
PremPRI (CV3) | 0.61 | 0.87 | 0.76 | 0.76 | 0.45 |
mCSM-NA | 0.24 * | 5.41 | 0.56 * | 0.60 | 0.22 |
FoldX | 0.20 * | 1.57 | 0.53 * | 0.59 | 0.24 |
PrabHot | - | - | 0.58 * | 0.61 | 0.26 |
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Zhang, N.; Lu, H.; Chen, Y.; Zhu, Z.; Yang, Q.; Wang, S.; Li, M. PremPRI: Predicting the Effects of Missense Mutations on Protein–RNA Interactions. Int. J. Mol. Sci. 2020, 21, 5560. https://doi.org/10.3390/ijms21155560
Zhang N, Lu H, Chen Y, Zhu Z, Yang Q, Wang S, Li M. PremPRI: Predicting the Effects of Missense Mutations on Protein–RNA Interactions. International Journal of Molecular Sciences. 2020; 21(15):5560. https://doi.org/10.3390/ijms21155560
Chicago/Turabian StyleZhang, Ning, Haoyu Lu, Yuting Chen, Zefeng Zhu, Qing Yang, Shuqin Wang, and Minghui Li. 2020. "PremPRI: Predicting the Effects of Missense Mutations on Protein–RNA Interactions" International Journal of Molecular Sciences 21, no. 15: 5560. https://doi.org/10.3390/ijms21155560