Molecular‐Dynamics‐Simulation‐Directed Rational Design of Nanoreceptors with Targeted Affinity

Sun, Xiaohuan; Riccardi, Laura; Biasi, Federico De; Rastrelli, Federico; Vivo, Marco De; Mancin, Fabrizio

doi:10.1002/anie.201902316

Cited by 32 publications

(38 citation statements)

References 25 publications

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“…The molecular recognition properties of these particles are dictated by the chemical structure of the coating ligands, which form self-organized and multivalent binding sites for the guest species [19], a feature crucial for nanoparticle colloidal stability [20,21]. The surface of the nanoparticles interfaces with the external environment, and appropriately engineered surfaces can be used to regulate interactions between nanoparticles and biomolecules [22][23][24] driven by non-covalent interactions [9,25].…”

Section: Introductionmentioning

confidence: 99%

Role of Ionic Strength in the Formation of Stable Supramolecular Nanoparticle–Protein Conjugates for Biosensing

Brancolini

Rotello

Corni

2022

IJMS

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Monolayer-protected gold nanoparticles (AuNPs) exhibit distinct physical and chemical properties depending on the nature of the ligand chemistry. A commonly employed NP monolayer comprises hydrophobic molecules linked to a shell of PEG and terminated with functional end group, which can be charged or neutral. Different layers of the ligand shell can also interact in different manners with proteins, expanding the range of possible applications of these inorganic nanoparticles. AuNP-fluorescent Green Fluorescent Protein (GFP) conjugates are gaining increasing attention in sensing applications. Experimentally, their stability is observed to be maintained at low ionic strength conditions, but not at physiologically relevant conditions of higher ionic strength, limiting their applications in the field of biosensors. While a significant amount of fundamental work has been done to quantify electrostatic interactions of colloidal nanoparticle at the nanoscale, a theoretical description of the ion distribution around AuNPs still remains relatively unexplored. We perform extensive atomistic simulations of two oppositely charged monolayer-protected AuNPs interacting with fluorescent supercharged GFPs co-engineered to have complementary charges. These simulations were run at different ionic strengths to disclose the role of the ionic environment on AuNP–GFP binding. The results highlight the capability of both AuNPs to intercalate ions and water molecules within the gold–sulfur inner shell and the different tendency of ligands to bend inward allowing the protein to bind not only with the terminal ligands but also the hydrophobic alkyl chains. Different binding stability is observed in the two investigated cases as a function of the ligand chemistry.

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Section: Introductionmentioning

confidence: 99%

Role of Ionic Strength in the Formation of Stable Supramolecular Nanoparticle–Protein Conjugates for Biosensing

Brancolini

Rotello

Corni

2022

IJMS

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“…The final binding pose is depicted in Figure 5c. This event resembles studies [48] on formation of transient protein like binding pocket; mimicking protein-ligand recognition mechanism formed by functionalized monolayer protected gold nanocluster or that for designing nanoreceptors with targeted affinity [49]. The same plots are produced for H 3 to disclose the ligands forming direct contact with H 3 , namely P close lig H3 in Figure 6d and to distinguish the ones forming contact points simultaneously (Figure 6e and Figure S5c,d) over the simulation.…”

Section: H(mentioning

confidence: 59%

Section: H(mentioning

confidence: 74%

Molecular Dynamics Simulations of a Catalytic Multivalent Peptide–Nanoparticle Complex

Dutta

Corni

Brancolini

2021

IJMS

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Molecular modeling of a supramolecular catalytic system is conducted resulting from the assembling between a small peptide and the surface of cationic self-assembled monolayers on gold nanoparticles, through a multiscale iterative approach including atomistic force field development, flexible docking with Brownian Dynamics and µs-long Molecular Dynamics simulations. Self-assembly is a prerequisite for the catalysis, since the catalytic peptides do not display any activity in the absence of the gold nanocluster. Atomistic simulations reveal details of the association dynamics as regulated by defined conformational changes of the peptide due to peptide length and sequence. Our results show the importance of a rational design of the peptide to enhance the catalytic activity of peptide–nanoparticle conjugates and present a viable computational approach toward the design of enzyme mimics having a complex structure–function relationship, for technological and nanomedical applications.

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“…PEGylation has been proposed for virtually every one of the nanoparticle types described in the previous section. This includes PEGylated carbon nanotubes (Pennetta et al, 2020), gold nanoparticles (Oroskar et al, 2016;Lin et al, 2017;Sun et al, 2019), silver nanoparticle (Pinzaru et al, 2018), silver-graphene nanoparticles (Habiba et al, 2015), nano-graphene (Zhang et al, 2014;Zhang Z. et al, 2020;Mahdavi et al, 2020), lipid micelles (Arleth et al, 2005;Viitala et al, 2019; Figure 6D), nanodiscs (Zhang et al, 2014), dendrimers (Kojima et al, 2000;Larson, 2009, 2011;Zhang et al, 2014), and a topic covered comprehensively in our previous review, liposomes (Bunker et al, 2016; Figures 6A,C).…”

Section: Nanoparticle Design and Functionmentioning

confidence: 97%

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

Bunker

Róg

2020

Front. Mol. Biosci.

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In this review, we outline the growing role that molecular dynamics simulation is able to play as a design tool in drug delivery. We cover both the pharmaceutical and computational backgrounds, in a pedagogical fashion, as this review is designed to be equally accessible to pharmaceutical researchers interested in what this new computational tool is capable of and experts in molecular modeling who wish to pursue pharmaceutical applications as a context for their research. The field has become too broad for us to concisely describe all work that has been carried out; many comprehensive reviews on subtopics of this area are cited. We discuss the insight molecular dynamics modeling has provided in dissolution and solubility, however, the majority of the discussion is focused on nanomedicine: the development of nanoscale drug delivery vehicles. Here we focus on three areas where molecular dynamics modeling has had a particularly strong impact: (1) behavior in the bloodstream and protective polymer corona, (2) Drug loading and controlled release, and (3) Nanoparticle interaction with both model and biological membranes. We conclude with some thoughts on the role that molecular dynamics simulation can grow to play in the development of new drug delivery systems.

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Molecular‐Dynamics‐Simulation‐Directed Rational Design of Nanoreceptors with Targeted Affinity

Cited by 32 publications

References 25 publications

Role of Ionic Strength in the Formation of Stable Supramolecular Nanoparticle–Protein Conjugates for Biosensing

Role of Ionic Strength in the Formation of Stable Supramolecular Nanoparticle–Protein Conjugates for Biosensing

Molecular Dynamics Simulations of a Catalytic Multivalent Peptide–Nanoparticle Complex

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

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