<p>Is anyone aware of a tool which allows one to apply the concept of &quot;mutation hotspots&quot; to 3D protein structures? It is common to define mutation hot spots at the DNA level where we define the hotspot as a region of DNA sequence with recurrent mutations. But what if we want to know if some mutations are &quot;geographically&quot; co-located in the 3D protein structure (e.g., in the same pocket) but not necessarily &quot;sequentially&quot; co-located. Even without pre-defined concepts of &quot;pockets&quot; if a protein structure is known then it should be possible to define some concept of physical distance between residues. Any suggestions?</p>

It looks like maybe the tool '<a href="http://mupit.icm.jhu.edu/">MuPIT</a>' was created to help researchers address this question. From the <a href="http://www.ncbi.nlm.nih.gov/pubmed/23793516">Pubmed Abtract</a>:

> MuPIT interactive: webserver for mapping variant positions to annotated, interactive 3D structures.

> Mutation position imaging toolbox (MuPIT) interactive is a browser-based application for single-nucleotide variants (SNVs), which automatically maps the genomic coordinates of SNVs onto the coordinates of available three-dimensional (3D) protein structures. The application is designed for interactive browser-based visualization of the putative functional relevance of SNVs by biologists who are not necessarily experts either in bioinformatics or protein structure. Users may submit batches of several thousand SNVs and review all protein structures that cover the SNVs, including available functional annotations such as binding sites, mutagenesis experiments, and common polymorphisms. Multiple SNVs may be mapped onto each structure, enabling 3D visualization of SNV clusters and their relationship to functionally annotated positions. We illustrate the utility of MuPIT interactive in rationalizing the impact of selected polymorphisms in the PharmGKB database, somatic mutations identified in the Cancer Genome Atlas study of invasive breast carcinomas, and rare variants identified in the exome sequencing project.