As of version 2.0 (to be released soon), DSSR has a new module for in silico base mutations that is context sensitive. Powered by the DSSR analysis engine, the module allows users to perform base mutations in unprecedented flexibility and convenance. Here are some examples:
- Mutate all bases in hairpin loops to a specific base (e.g., G)
- Mutate all non-stem bases to a specific base (e.g., U)
- Mutate bases 2-12 to a specific base (e.g., A) regardless of context
- Mutate bases 1-10 in a given structure to a new sequence (e.g., AUAUAUAUAU)
- Mutate all bases of the same type to another (e.g., A to G)
- Mutate all bases of the same type to another (e.g., C to U) except for some nucleotides
- Mutate all G-C Watson-Crick (WC) pairs to C-G WC pairs, and A-U to U-A
- Mutate all G-tetrads in G-quadruplexes to non-G-tetrads (e.g., U-tetrads)
By default, the mutation preserves both the geometry of the sugar-phosphate backbone and the base reference frame (position and orientation). As a result, re-analyzing the mutated model gives the same base-pair and step parameters as those of the original structure.
Over the years, the 3DNA mutate bases program has been cited in the literature and patent, including the following ones:
- Howe, John A., et al. Selective small-molecule inhibition of an RNA structural element. Nature 526.7575 (2015): 672-677.
- Wang, Hao, et al. Dual-targeting small-molecule inhibitors of the Staphylococcus aureus FMN riboswitch disrupt riboflavin homeostasis in an infectious setting. Cell Chemical Biology 24.5 (2017): 576-588.
- AlQuraishi, Mohammed, and Harley H. McAdams. Three enhancements to the inference of statistical protein‐DNA potentials. Proteins: Structure, Function, and Bioinformatics 81.3 (2013): 426-442.
- Wang, Harris, Sagi Shapira, and Victoria Stockman. High-throughput strategy for dissecting mammalian genetic interactions. U.S. Patent Application No. 15/747,677.
The DSSR mutation module has completely obsoleted the mutate_bases program distributed in 3DNA v2.x. In addition to serving as a drop-in replacement of mutate_bases, the DSSR approach offers much more features and versatility: it is simply better.
