Predicting aptamer sequences that interact with target proteins using an aptamer-protein interaction classifier and a Monte Carlo tree search approach

PLoS One. 2021 Jun 25;16(6):e0253760. doi: 10.1371/journal.pone.0253760. eCollection 2021.

Abstract

Oligonucleotide-based aptamers, which have a three-dimensional structure with a single-stranded fragment, feature various characteristics with respect to size, toxicity, and permeability. Accordingly, aptamers are advantageous in terms of diagnosis and treatment and are materials that can be produced through relatively simple experiments. Systematic evolution of ligands by exponential enrichment (SELEX) is one of the most widely used experimental methods for generating aptamers; however, it is highly expensive and time-consuming. To reduce the related costs, recent studies have used in silico approaches, such as aptamer-protein interaction (API) classifiers that use sequence patterns to determine the binding affinity between RNA aptamers and proteins. Some of these methods generate candidate RNA aptamer sequences that bind to a target protein, but they are limited to producing candidates of a specific size. In this study, we present a machine learning approach for selecting candidate sequences of various sizes that have a high binding affinity for a specific sequence of a target protein. We applied the Monte Carlo tree search (MCTS) algorithm for generating the candidate sequences using a score function based on an API classifier. The tree structure that we designed with MCTS enables nucleotide sequence sampling, and the obtained sequences are potential aptamer candidates. We performed a quality assessment using the scores of docking simulations. Our validation datasets revealed that our model showed similar or better docking scores in ZDOCK docking simulations than the known aptamers. We expect that our method, which is size-independent and easy to use, can provide insights into searching for an appropriate aptamer sequence for a target protein during the simulation step of SELEX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide* / chemistry
  • Aptamers, Nucleotide* / genetics
  • Computer Simulation*
  • Machine Learning*
  • Models, Chemical*
  • Molecular Docking Simulation
  • Monte Carlo Method
  • Proteins / chemistry*
  • Sequence Analysis, RNA*

Substances

  • Aptamers, Nucleotide
  • Proteins

Grants and funding

This work was supported by an Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT) (No. 2020-0- 01450, Artificial Intelligence Convergence Research Center [Pusan National University]) and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1A2C2010775) to GS. NuclixBio provided support in the form of salaries for authors [G.H.J. and H.Y.K.]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘Author Contributions’ section.