Abstracts
A novel rotamer library for nucleic acids enables the design of protein-nucleic acid complexes with the protein design software MUMBO
Presenter: Marharyta Makarova (marharyta.makarova@fau.de)
Authors:
Marharyta Makarova¹; Dr. Martin T. Stiebritz¹; Prof. Dr. Beatrix Suess²; Prof. Dr. Yves A. Muller¹
¹ FAU Erlangen-Nuremberg; ² Technical University Darmstadt
Current AI-tools for designing macromolecules have been struggling with DNA and RNA structure prediction and design, as the amount of respective experimental data available for training is significantly lower than that of proteins. Therefore, developing alternative approaches remains of interest. MUMBO is a program that allows designing protein-protein interactions and protein-ligand binding pockets by means of side-chain packing algorithms, where alternative amino acids and their rotamers are generated from libraries on a fixed backbone and the most favourable ones are selected based on the lowest overall energy. In order to extend MUMBO capabilities to designing nucleic acids, a nucleotide rotamer library is needed. Based on statistical analysis of pseudorotational angles and dihedral angles of more than 175,000 nucleotides from experimental structures deposited with the PDB database, a discrete pseudorotational angle-dependent nucleotide-specific rotamer library was derived. We validated the library by rebuilding more than 20,000 nucleotides in a custom dataset and showed that it allows modelling nucleotides with accuracies even slightly better than for amino acids. The implementation of the novel nucleotide rotamer library in MUMBO enables modelling and designing DNA and RNA sequences on a fixed backbone together with protein-nucleic acid interaction interfaces.