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172 results on '"Salvador, Armindo"'

10. Analysis of the equilibrium distribution of Ligands in Heterogeneous Media – Approaches and pitfalls

Author

Moreno, Maria João, Loura, Luís M. S., M. Martins, Jorge, Salvador, Armindo, and Velazquez-Campoy, Adrian

Subjects
Binding affinity, Lipid bilayers, Biomembranes, Stern–Volmer plots, Proteins, Scatchard plots, Partition coefficient
Abstract

The equilibrium distribution of small molecules (ligands) between binding agents in heterogeneous media is an important property that determines their activity. Heterogeneous systems containing proteins and lipid membranes are particularly relevant due to their prevalence in biological systems, and their importance to ligand distribution, which, in turn, is crucial to ligand’s availability and biological activity. In this work, we review several approaches and formalisms for the analysis of the equilibrium distribution of ligands in the presence of proteins, lipid membranes, or both. Special attention is given to common pitfalls in the analysis, with the establishment of the validity limits for the distinct approaches. Due to its widespread use, special attention is given to the characterization of ligand binding through the analysis of Stern–Volmer plots of protein fluorescence quenching. Systems of increasing complexity are considered, from proteins with single to multiple binding sites, from ligands interacting with proteins only to biomembranes containing lipid bilayers and membrane proteins. A new formalism is proposed, in which ligand binding is treated as a partition process, while considering the saturation of protein binding sites. This formalism is particularly useful for the characterization of interaction with membrane proteins. info:eu-repo/semantics/publishedVersion

Published
2022

29. Modeling Gd3+Complexes for Molecular Dynamics Simulations: Toward a Rational Optimization of MRI Contrast Agents

Author

Oliveira, Alexandre C., Filipe, Hugo A. L., Ramalho, João P. Prates, Salvador, Armindo, Geraldes, Carlos F. G. C., Moreno, Maria João, and Loura, Luís M. S.

Abstract

The correct parametrization of lanthanide complexes is of the utmost importance for their characterization using computational tools such as molecular dynamics simulations. This allows the optimization of their properties for a wide range of applications, including medical imaging. Here we present a systematic study to establish the best strategies for the correct parametrization of lanthanide complexes using [Gd(DOTA)]−as a reference, which is used as a contrast agent in MRI. We chose the bonded model to parametrize the lanthanide complexes, which is especially important when considering the study of the complex as a whole (e.g., for the study of the dynamics of its interaction with proteins or membranes). We followed two strategies: a so-called heuristic approach employing strategies already published by other authors and another based on the more recent MCPB.py tool. Adjustment of the Lennard-Jones parameters of the metal was required. The final topologies obtained with both strategies were able to reproduce the experimental ion to oxygen distance, vibrational frequencies, and other structural properties. We report a new strategy to adjust the Lennard-Jones parameters of the metal ion in order to capture dynamic properties such as the residence time of the capping water (τm). For the first time, the correct assessment of the τmvalue for Gd-based complexes was possible by recording the dissociative events over up to 10 μs all-atom simulations. The MCPB.py tool allowed the accurate parametrization of [Gd(DOTA)]−in a simpler procedure, and in this case, the dynamics of the water molecules in the outer hydration sphere was also characterized. This sphere was divided into the first hydration layer, an intermediate region, and an outer hydration layer, with a residence time of 18, 10 and 19 ps, respectively, independent of the nonbonded parameters chosen for Gd3+. The Lennard-Jones parameters of Gd3+obtained here for [Gd(DOTA)]−may be used with similarly structured gadolinium MRI contrast agents. This allows the use of molecular dynamics simulations to characterize and optimize the contrast agent properties. The characterization of their interaction with membranes and proteins will permit the design of new targeted contrast agents with improved pharmacokinetics.

Published
2022
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41. Kinetic Modelling of Reactive Chemical Species in Ancient Oceans: The Evolutionary Origin of Oxidative Stress

Author

Pais, Ricardo Jorge, Salvador, Armindo, Ferreira, António E., and Antunes, Fernando

Abstract

By simulation of ancient oceans chemical environment exposed to UV, we estimate the average daily ROS concentration and the pseudo 1 st order rate constant for the oxidation of biomolecules in the photic (0-50 m deep) and aphotic (>200m deep) zones. We also present an estimation of antioxidant proteins times of appearance in evolution.

Published
2010
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