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. 2021 Jan 8;49(D1):D475-D479.
doi: 10.1093/nar/gkaa925.

ThermoMutDB: a thermodynamic database for missense mutations

Joicymara S Xavier  1   2 , Thanh-Binh Nguyen  3 , Malancha Karmarkar  3   4 , Stephanie Portelli  3   4 , Pâmela M Rezende  2 , João P L Velloso  2 , David B Ascher  3   4   5 , Douglas E V Pires  3   4   6
Affiliations

ThermoMutDB: a thermodynamic database for missense mutations

Joicymara S Xavier et al. Nucleic Acids Res. .

Abstract

Proteins are intricate, dynamic structures, and small changes in their amino acid sequences can lead to large effects on their folding, stability and dynamics. To facilitate the further development and evaluation of methods to predict these changes, we have developed ThermoMutDB, a manually curated database containing >14,669 experimental data of thermodynamic parameters for wild type and mutant proteins. This represents an increase of 83% in unique mutations over previous databases and includes thermodynamic information on 204 new proteins. During manual curation we have also corrected annotation errors in previously curated entries. Associated with each entry, we have included information on the unfolding Gibbs free energy and melting temperature change, and have associated entries with available experimental structural information. ThermoMutDB supports users to contribute to new data points and programmatic access to the database via a RESTful API. ThermoMutDB is freely available at: http://biosig.unimelb.edu.au/thermomutdb.

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Figures

Graphical Abstract
Graphical Abstract
ThermoMutDB is an online resource associating effects of missense mutations on protein thermodynamics.
Figure 1.
Figure 1.
ThermoMutDB workflow for data acquisition and processing. The development workflow is divided into three steps: (A) verification of previously available mutation thermodynamics information (B) collection and manual curation of new data and (C) data aggregation and mutation annotation.
Figure 2.
Figure 2.
ThermoMutDB web interface search and results pages. (A) ThermoMutDB offers 12 query modes, with detailed information available about each query type through the ‘Help’ page at the top navigation bar and through on-page help in the form of question mark tooltips. (B) The general layout of the result page, showing a summary of information for each entry as well as detailed view.
Figure 3.
Figure 3.
Composition of ThermoMutDB entries. (A) depicts the distribution of phylogenetic kingdoms of proteins in the database. (B) highlights the distribution of thermodynamic effects of mutation in the database, given as the variation in Gibbs Free Energy (ΔΔG). (C) Experimental variability of mutation assessed under different conditions and groups. (D) Distribution of mutations in ThermoMutDB based on type (mutation to alanine/non-alanine), their location and residue environment.
See this image and copyright information in PMC

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