Insight into uranyl binding by cyclic peptides from molecular dynamics and density functional theory

Platts, James A. ORCID: https://orcid.org/0000-0002-1008-6595 and Tolbatov, Iogann 2025. Insight into uranyl binding by cyclic peptides from molecular dynamics and density functional theory. Journal of Inorganic Biochemistry 264 , 112793. 10.1016/j.jinorgbio.2024.112793

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview

Abstract

It is a challenging task to develop uranyl-chelating agents based on peptide chemistry. A recently developed cationic dummy atom model of uranyl in conjunction with the classical molecular dynamics simulation presents a helpful utility to study the chelation of uranyl by peptides with a low computational cost. In the present study, it was used to describe the chelation of uranyl by the cyclic decapeptide with 4 Glu residues cyc-GluArgGluProGlyGluTrpGluProGly and its derivatives containing two phosphorylated serines in place of two Glu, termed pS16, pS18, pS38, and pS68. The obtained structures were further studied by density functional theory (DFT) and subsequent density analysis. We show that a combination of steered molecular dynamics and simulated annealing, using standard forcefields for peptide with the cationic dummy atom model of uranyl, can quickly and reliably obtain binding modes of uranyl-peptide complexes. Classical molecular dynamics simulation in explicit water produces geometry very close to the DFT-optimized structure. The presence of uranyl completely changes the conformation of these cyclic peptides from unstructured to organised. The simulation of a peptide with two uranyl units explained why only the 1:1 ratio of peptide and chelated-uranyl is observed experimentally in most cases, by the insufficiency of the anionic residues for the chelation of two UO22+ units, but that pS16 can accommodate two such units.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Publisher:	Elsevier
ISSN:	0162-0134
Funders:	European Union
Date of First Compliant Deposit:	3 January 2025
Date of Acceptance:	27 November 2024
Last Modified:	07 Jan 2025 10:45
URI:	https://orca.cardiff.ac.uk/id/eprint/174958

Actions (repository staff only)

Edit Item