Arbitrary Digital DNA Computing: A Programmable Molecular Perceptron Driven by Lambda Exonuclease for Lighting up Concatenated Circuits

ACS Appl Mater Interfaces. 2024 May 15;16(19):24372-24383. doi: 10.1021/acsami.4c03486. Epub 2024 Apr 30.

Abstract

DNA circuits, as a type of biochemical system, have the capability to synchronize the perception of molecular information with a chemical reaction response and directly process the molecular characteristic information in biological activities, making them a crucial area in molecular digital computing and smart bioanalytical applications. Instead of cascading logic gates, the traditional research approach achieves multiple logic operations which limits the scalability of DNA circuits and increases the development costs. Based on the interface reaction mechanism of Lambda exonuclease, the molecular perceptron proposed in this study, with the need for only adjusting weight and bias parameters to alter the corresponding logic expressions, enhances the versatility of the molecular circuits. We also establish a mathematical model and an improved heuristic algorithm for solving weights and bias parameters for arbitrary logic operations. The simulation and FRET experiment results of a series of logic operations demonstrate the universality of molecular perceptron. We hope the proposed molecular perceptron can introduce a new design paradigm for molecular circuits, fostering innovation and development in biomedical research related to biosensing, targeted therapy, and nanomachines.

Keywords: DNA circuits; Lambda exonuclease; hydrolysis characteristic; molecular digital computation; molecular perceptron.

MeSH terms

  • Algorithms
  • Bacteriophage lambda / genetics
  • Biosensing Techniques / methods
  • Computers, Molecular*
  • DNA* / chemistry
  • DNA* / metabolism
  • Exodeoxyribonucleases / chemistry
  • Exodeoxyribonucleases / metabolism
  • Exonucleases / metabolism
  • Fluorescence Resonance Energy Transfer