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SDM: a server for predicting effects of mutations on protein stability.

Arun Prasad Pandurangan | Bernardo Ochoa-Montaño | David B Ascher | Tom L Blundell
Nucleic acids research | 2017

Here, we report a webserver for the improved SDM, used for predicting the effects of mutations on protein stability. As a pioneering knowledge-based approach, SDM has been highlighted as the most appropriate method to use in combination with many other approaches. We have updated the environment-specific amino-acid substitution tables based on the current expanded PDB (a 5-fold increase in information), and introduced new residue-conformation and interaction parameters, including packing density and residue depth. The updated server has been extensively tested using a benchmark containing 2690 point mutations from 132 different protein structures. The revised method correlates well against the hypothetical reverse mutations, better than comparable methods built using machine-learning approaches, highlighting the strength of our knowledge-based approach for identifying stabilising mutations. Given a PDB file (a Protein Data Bank file format containing the 3D coordinates of the protein atoms), and a point mutation, the server calculates the stability difference score between the wildtype and mutant protein. The server is available at http://structure.bioc.cam.ac.uk/sdm2.

Pubmed ID: 28525590

Research resources used in this publication

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Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MR/M026302/1
  • Agency: Medical Research Council, United Kingdom
    Id: MR/N501864/1

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This is a list of tools and resources that we have found mentioned in this publication.


HOMSTRAD - Homologous Structure Alignment Database (tool)

RRID:SCR_006544

A curated database of structure-based alignments for homologous protein families. All known protein structure are clustered into homologous families (i.e., common ancestry), and the sequences of representative members of each family are aligned on the basis of their 3D structures using the programs MNYFIT, STAMP and COMPARER. These structure-based alignments are annotated with JOY and examined individually.

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CATH: Protein Structure Classification (tool)

RRID:SCR_007583

CATH is a hierarchical classification of protein domain structures, which clusters proteins at four major levels: Class (C), Architecture (A), Topology (T) and Homologous superfamily (H). The boundaries and assignments for each protein domain are determined using a combination of automated and manual procedures which include computational techniques, empirical and statistical evidence, literature review and expert analysis Users can search CATH by ID/Sequence/text. They can also browse CATH from the top of the hierarchy, or download CATH data.

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