A fully atomistic (AT) modeling of biological macromolecules at relevant length- and time-scales is often cumbersome or not even desirable, both in terms of computational effort required and a posteriori analysis. This difficulty can be overcome with the use of multiresolution models, in which different regions of the same system are concurrently described at different levels of detail. In enzymes, computationally expensive AT detail is crucial in the modeling of the active site in order to capture, for example, the chemically subtle process of ligand binding. In contrast, important yet more collective properties of the remainder of the protein can be reproduced with a coarser description. In the present work, we demonstrate the effectiveness of this approach through the calculation of the binding free energy of hen egg white lysozyme with the inhibitor di-N-acetylchitotriose. Particular attention is payed to the impact of the mapping, that is, the selection of AT and coarse-grained residues, on the binding free energy. It is shown that, in spite of small variations of the binding free energy with respect to the active site resolution, the separate contributions coming from different energetic terms (such as electrostatic and van der Waals interactions) manifest a stronger dependence on the mapping, thus pointing to the existence of an optimal level of intermediate resolution.

Ligand-protein interactions in lysozyme investigated through a dual-resolution model / Fiorentini, Raffaele; Kremer, Kurt; Potestio, Raffaello. - In: PROTEINS. - ISSN 0887-3585. - 2020:(2020), pp. 1-10. [10.1002/prot.25954]

Ligand-protein interactions in lysozyme investigated through a dual-resolution model

Potestio, Raffaello
2020-01-01

Abstract

A fully atomistic (AT) modeling of biological macromolecules at relevant length- and time-scales is often cumbersome or not even desirable, both in terms of computational effort required and a posteriori analysis. This difficulty can be overcome with the use of multiresolution models, in which different regions of the same system are concurrently described at different levels of detail. In enzymes, computationally expensive AT detail is crucial in the modeling of the active site in order to capture, for example, the chemically subtle process of ligand binding. In contrast, important yet more collective properties of the remainder of the protein can be reproduced with a coarser description. In the present work, we demonstrate the effectiveness of this approach through the calculation of the binding free energy of hen egg white lysozyme with the inhibitor di-N-acetylchitotriose. Particular attention is payed to the impact of the mapping, that is, the selection of AT and coarse-grained residues, on the binding free energy. It is shown that, in spite of small variations of the binding free energy with respect to the active site resolution, the separate contributions coming from different energetic terms (such as electrostatic and van der Waals interactions) manifest a stronger dependence on the mapping, thus pointing to the existence of an optimal level of intermediate resolution.
2020
Fiorentini, Raffaele; Kremer, Kurt; Potestio, Raffaello
Ligand-protein interactions in lysozyme investigated through a dual-resolution model / Fiorentini, Raffaele; Kremer, Kurt; Potestio, Raffaello. - In: PROTEINS. - ISSN 0887-3585. - 2020:(2020), pp. 1-10. [10.1002/prot.25954]
File in questo prodotto:
File Dimensione Formato  
ERC_2020_Fiorentini_PROTEINS.pdf

accesso aperto

Tipologia: Versione editoriale (Publisher’s layout)
Licenza: Creative commons
Dimensione 2.25 MB
Formato Adobe PDF
2.25 MB Adobe PDF Visualizza/Apri

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/11572/269298
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact