2020/02/12 by Raffaele Fiorentini, Kurt Kremer, Fiorentini, Raffaele +3
Biochemistry, Genetics and Molecular Biology · Chemistry · Materials Science · #Biological Physics (physics.bio-ph) #Biomolecules (q-bio.BM) #Enzyme Structure and Function #FOS: Biological sciences #FOS: Physical sciences #Mass Spectrometry Techniques and Applications #Protein Structure and Dynamics #Soft Condensed Matter (cond-mat.soft)
paper · pdf · doi:10.48550/arxiv.2002.05263
openalex publication_date 2020/02/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
A fully atomistic modelling of biological macromolecules at relevant length-\nand time-scales is often cumbersome or not even desirable, both in terms of\ncomputational effort required and it a posteriori analysis. This difficulty can\nbe overcome with the use of multi-resolution models, in which different regions\nof the same system are concurrently described at different levels of detail. In\nenzymes, computationally expensive atomistic detail is crucial in the modelling\nof the active site in order to capture e.g. the chemically subtle process of\nligand binding. In contrast, important yet more collective properties of the\nremainder of the protein can be reproduced with a coarser description. In the\npresent work, we demonstrate the effectiveness of this approach through the\ncalculation of the binding free energy of hen egg white lysozyme (HEWL) with\nthe inhibitor di-N-acetylchitotriose. Particular attention is posed to the\nimpact of the mapping, i.e. the selection of atomistic and coarse-grained\nresidues, on the binding free energy. It is shown that, in spite of small\nvariations of the binding free energy with respect to the active site\nresolution, the separate contributions coming from different energetic terms\n(such as electrostatic and van der Waals interactions) manifest a stronger\ndependence on the mapping, thus pointing to the existence of an optimal level\nof intermediate resolution.\n