Ribonucleic acid (RNA) plays a key regulatory role within the cell, cooperating with proteins to control the genome expression and several biological processes. Due to its characteristic structural features, this polymer can mold itself into different three-dimensional structures able to recognize target biomolecules with high affinity and specificity, thereby attracting the interest of drug developers and medicinal chemists. One successful example of the exploitation of RNA's structural and functional peculiarities is represented by aptamers, a class of therapeutic and diagnostic tools that can recognize and tightly bind several pharmaceutically relevant targets, ranging from small molecules to proteins, making use of the available structural and conformational freedom to maximize the complementarity with their interacting counterparts. In this scientific work, we present the first application of Supervised Molecular Dynamics (SuMD), an enhanced sampling Molecular Dynamics-based method for the study of receptor-ligand association processes in the nanoseconds timescale, to the study of recognition pathways between RNA aptamers and proteins, elucidating the main advantages and limitations of the technique while discussing its possible role in the rational design of RNA-based therapeutics.

Investigating RNA-protein recognition mechanisms through supervised molecular dynamics (SuMD) simulations

Matteo Pavan;Davide Bassani;Mattia Sturlese;Stefano Moro
2022

Abstract

Ribonucleic acid (RNA) plays a key regulatory role within the cell, cooperating with proteins to control the genome expression and several biological processes. Due to its characteristic structural features, this polymer can mold itself into different three-dimensional structures able to recognize target biomolecules with high affinity and specificity, thereby attracting the interest of drug developers and medicinal chemists. One successful example of the exploitation of RNA's structural and functional peculiarities is represented by aptamers, a class of therapeutic and diagnostic tools that can recognize and tightly bind several pharmaceutically relevant targets, ranging from small molecules to proteins, making use of the available structural and conformational freedom to maximize the complementarity with their interacting counterparts. In this scientific work, we present the first application of Supervised Molecular Dynamics (SuMD), an enhanced sampling Molecular Dynamics-based method for the study of receptor-ligand association processes in the nanoseconds timescale, to the study of recognition pathways between RNA aptamers and proteins, elucidating the main advantages and limitations of the technique while discussing its possible role in the rational design of RNA-based therapeutics.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3469384
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 5
social impact