A high-throughput and rapid computational method for screening of RNA post-transcriptional modifications that can be recognized by target proteins

Publication date: Available online 1 February 2018 Source:Methods Author(s): Asuka A. Orr, Juan C. Gonzalez-Rivera, Mark Wilson, P. Reena Bhikha, Daiqi Wang, Lydia M. Contreras, Phanourios Tamamis There are over 150 currently known, highly diverse chemically modified RNAs, which are dynamic, reversible, and can modulate RNA-protein interactions. Yet, little is known about the wealth of such interactions. This can be attributed to the lack of tools that allow the rapid study of all the potential RNA modifications that might mediate RNA-protein interactions. As a promising step toward this direction, here we present a computational protocol for the characterization of interactions between proteins and RNA containing post-transcriptional modifications. Given an RNA-protein complex structure, potential RNA modified ribonucleoside positions, and molecular mechanics parameters for capturing energetics of RNA modifications, our protocol operates in two stages. In the first stage, a decision-making tool, comprising short simulations and interaction energy calculations, performs a fast and efficient search in a high-throughput fashion, through a list of different types of RNA modifications categorized into trees according to their structural and physicochemical properties, and selects a subset of RNA modifications prone to interact with the target protein. In the second stage, RNA modifications that are selected as recognized by the protein are examined in-detail using all-at...
Source: Methods - Category: Molecular Biology Source Type: research