Metallo-enzymes are a large class of biomolecules promoting specialized chemical reactions. Quantum-classical quantum mechanics/molecular mechanics molecular dynamics, describing the metal site at quantum mechanics level, while accounting for the rest of system at molecular mechanics level, has an accessible time-scale limited by its computational cost. Hence, it must be integrated with classical molecular dynamics and enhanced sampling simulations to disentangle the functions of metallo-enzymes. In this review, we provide an overview of these computational methods and their capabilities. In particular, we will focus on some systems such as CYP19A1 a Fe-dependent enzyme involved in estrogen biosynthesis, and on Mg2+-dependent DNA/RNA processing enzymes/ribozymes and the spliceosome, a protein-directed ribozyme. This information may guide the discovery of drug-like molecules and genetic manipulation tools.

Can multiscale simulations unravel the function of metallo-enzymes to improve knowledge-based drug discovery? / Sgrignani, J.; Casalino, L.; Doro, F.; Spinello, A.; Magistrato, A.. - In: FUTURE MEDICINAL CHEMISTRY. - ISSN 1756-8919. - 11:7(2019), pp. 771-791. [10.4155/fmc-2018-0495]

Can multiscale simulations unravel the function of metallo-enzymes to improve knowledge-based drug discovery?

Casalino L.;Magistrato A.
2019

Abstract

Metallo-enzymes are a large class of biomolecules promoting specialized chemical reactions. Quantum-classical quantum mechanics/molecular mechanics molecular dynamics, describing the metal site at quantum mechanics level, while accounting for the rest of system at molecular mechanics level, has an accessible time-scale limited by its computational cost. Hence, it must be integrated with classical molecular dynamics and enhanced sampling simulations to disentangle the functions of metallo-enzymes. In this review, we provide an overview of these computational methods and their capabilities. In particular, we will focus on some systems such as CYP19A1 a Fe-dependent enzyme involved in estrogen biosynthesis, and on Mg2+-dependent DNA/RNA processing enzymes/ribozymes and the spliceosome, a protein-directed ribozyme. This information may guide the discovery of drug-like molecules and genetic manipulation tools.
https://europepmc.org/article/med/30938544
Sgrignani, J.; Casalino, L.; Doro, F.; Spinello, A.; Magistrato, A.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

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/20.500.11767/116690
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact