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Proposal of potentially stabilizing mutations.

Protposer is a protein stabilization tool that analyses PDB files and sequence databases in search for wild type amino acid residues providing opportunities for thermostabilization. Protposer proposes a list of point mutations that are likely to increase protein stability by at least 0.5 kcal/mol. To do so, it searches for divergences from ancestral or consensus sequences, from ideal alpha-helix composition or average solvent exposure of polar or apolar residues, and for the presence of cavities, electrostatic imbalance or acidic H-bonds. Protposer finds weak spots in the structure, generates and evaluates replacements, and estimates their probability of being stabilizing, using a machine learning logistic regression model.

Protposer users can indicate a PDB ID code or upload their own PDB file. The results are shown in an HTML summary, containing the proposed mutations, the reason why they are proposed, and how they scored for different features. The report is emailed to the address provided by the user and remains accessible in the server for 15 days.

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Thank you for using Protposer. Please, cite Garcia-Cebollada et al. (2022).