Bilkent University
Department of Computer Engineering
M.S.THESIS PRESENTATION
RNA X: MODELING RNA INTERACTIONS TO DESIGN BINDER RNA AND SIMULTANEOUSLY TARGET MULTIPLE MOLECULES OF DIFFERENT TYPES
Sobhan Shokoueiantabrizi
Master Student
(Supervisor: Assoc.Prof.Ercüment çiçek )
Computer Engineering Department
Bilkent University
Abstract: Interactions between RNA and proteins, other RNAs, or DNA regulate many cellular processes and underpin diverse therapeutic mechanisms. Modelling these interactions is therefore important for understanding biological systems and developing RNA-based therapeutics. However, designing an RNA that binds tightly and selectively to a chosen target remains challenging because the sequence space is vast and current experimental and computational methods are limited. Here we introduce RNA–X, the first foundation model for RNA interactions. RNA–X uses masked language modelling to support conditional RNA design, sequence optimization, and representation learning. It provides two new capabilities. First, it can design RNAs targeting proteins, other RNAs, or DNA. Second, it can design a single RNA against multiple targets simultaneously. Across extensive evaluations, RNA–X generates sequences with structural properties characteristic of natural RNAs and outperforms state-of-the-art methods on protein targets. Using molecular dynamics simulations and affinity predictors, we further show that RNA–X designs RNAs against therapeutically relevant molecules, including p53 and thrombin, and against targets with no available interaction data, such as SDAD1. We also design a completely new guide RNA that simultaneously binds bacterial DNA and the Cas9 protein. Its predicted binding energy is close to the value reported in the Protein Data Bank for the corresponding wild-type guide RNA. RNA–X has orders of magnitude fewer parameters than existing RNA foundation models. Nevertheless, its representations outperform those of these models across several downstream RNA interaction tasks.
DATE: October 01, Thursday @ 10:30
Place: EA 502