How to improve the modelling of proteins mutations? A preliminary assessment
Author and article information
Abstract
Several programs have been developed that are able to replace a residue with another one in a protein structure, but usually they are not able to simulate the short- and long-range effects of a real single point mutation. We tested if the approach of re-modelling the entire protein structure of a mutant protein using the wild type structure as a template can correctly reproduce the structural features of mutant proteins. To do this, we selected a benchmark of 4 different families of proteins for which a large group of mutants are available in the PDB database and we used MODELLER by applying different modelling strategies. Our results showed that different starting templates of the same wild type protein can affect the structures of the mutants, and that often structural peculiarities attributed to the effect of the mutations are strictly related to low quality electron density or alterations in the quality parameters used to evaluate the proteins. In general, the standard modelling procedure allows creating mutants more similar to the wild type protein than to the mutant one, but we devised possible suggestions to improve the ability of this approach to predict the effects of mutations on protein structure.
Cite this as
2018. How to improve the modelling of proteins mutations? A preliminary assessment. PeerJ Preprints 6:e27326v1 https://doi.org/10.7287/peerj.preprints.27326v1Author comment
This is an abstract which has been accepted for the BBCC2018 Conference
Sections
Additional Information
Competing Interests
The authors declare that they have no competing interests.
Author Contributions
Carolina Napoli performed the experiments, analyzed the data, prepared figures and/or tables, approved the final draft.
Anna Marabotti conceived and designed the experiments, contributed reagents/materials/analysis tools, prepared figures and/or tables, authored or reviewed drafts of the paper, approved the final draft.
Data Deposition
The following information was supplied regarding data availability:
The raw data/code is included in the manuscript.
Funding
This work was supported by University of Salerno (FARB-ORSA161582 and 170308) and by MIUR-Italian Ministry of University and Research (FFABR2017) (to A.M) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
