Image and Signal Processing Group, Department of Computer Science, Leipzig University, Augustusplatz 10, 04109 Leipzig, Germany.
Vanderbilt University, Center for Structural Biology, 465 21st Ave South, Nashville, TN 37232, USA.
Nucleic Acids Res. 2024 Jul 5;52(W1):W132-W139. doi: 10.1093/nar/gkae301.
The possible effects of mutations on stability and function of a protein can only be understood in the context of protein 3D structure. The MutationExplorer webserver maps sequence changes onto protein structures and allows users to study variation by inputting sequence changes. As the user enters variants, the 3D model evolves, and estimated changes in energy are highlighted. In addition to a basic per-residue input format, MutationExplorer can also upload an entire replacement sequence. Previously the purview of desktop applications, such an upload can back-mutate PDB structures to wildtype sequence in a single step. Another supported variation source is human single nucelotide polymorphisms (SNPs), genomic coordinates input in VCF format. Structures are flexibly colorable, not only by energetic differences, but also by hydrophobicity, sequence conservation, or other biochemical profiling. Coloring by interface score reveals mutation impacts on binding surfaces. MutationExplorer strives for efficiency in user experience. For example, we have prepared 45 000 PDB depositions for instant retrieval and initial display. All modeling steps are performed by Rosetta. Visualizations leverage MDsrv/Mol*. MutationExplorer is available at: http://proteinformatics.org/mutation_explorer/.
只有在了解蛋白质 3D 结构的情况下，才能理解突变对蛋白质稳定性和功能的可能影响。MutationExplorer 网络服务器将序列变化映射到蛋白质结构上，并允许用户通过输入序列变化来研究变异。随着用户输入变体，3D 模型会不断演变，并突出显示能量估计的变化。除了基本的逐残基输入格式外，MutationExplorer 还可以上传整个替换序列。以前，这种上传只能在单个步骤中将 PDB 结构反向突变回野生型序列，这是桌面应用程序的权限。另一个支持的变异源是人类单核苷酸多态性 (SNP)，以 VCF 格式输入的基因组坐标。结构可以灵活地进行颜色编码，不仅可以根据能量差异，还可以根据疏水性、序列保守性或其他生化特征进行颜色编码。通过界面得分进行颜色编码可以揭示突变对结合表面的影响。MutationExplorer 致力于提高用户体验的效率。例如，我们已经准备了 45000 个 PDB 存储库，以便即时检索和初始显示。所有建模步骤均由 Rosetta 执行。可视化利用 MDsrv/Mol*。MutationExplorer 可在：http://proteinformatics.org/mutation_explorer/。
