Computational screening of nanoparticles coupling to Aβ40 peptides and fibrils

Sen, Shamik; Vuković, Lela

doi:10.1038/s41598-019-52594-8

Cited by 11 publications

(10 citation statements)

References 39 publications

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“…The simulations showed that Au-NPs can influence the conformational change of the peptides and reduce inter-peptide interactions which can in turn prevent the β-Sheet formation of Aβ peptides and prolong the progress of Aβ aggregation. The interaction of NPs covered with different types of ligands (i.e., positively and negatively charged, peptide, and synthetic inhibitor ligands) with Aβ40 peptides and their fibrils were also investigated using MD [547]. The simulations revealed that the peptide-NPs and negatively charged-NPs attached to the free peptides and fibril tips, respectively, which can potentially restrict peptide fibrillization and fibril growth.…”

Section: Interactions With Viruses and Biomacromoleculesmentioning

confidence: 99%

“…The simulations revealed that the peptide-NPs and negatively charged-NPs attached to the free peptides and fibril tips, respectively, which can potentially restrict peptide fibrillization and fibril growth. Positively charged NPs, on the other hand, attached to the peptide and fibril surface and deformed it [547].…”

Section: Interactions With Viruses and Biomacromoleculesmentioning

confidence: 99%

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Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

et al. 2020

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Molecular dynamics (MD) simulations have become increasingly useful in the modern drug development process. In this review, we give a broad overview of the current application possibilities of MD in drug discovery and pharmaceutical development. Starting from the target validation step of the drug development process, we give several examples of how MD studies can give important insights into the dynamics and function of identified drug targets such as sirtuins, RAS proteins, or intrinsically disordered proteins. The role of MD in antibody design is also reviewed. In the lead discovery and lead optimization phases, MD facilitates the evaluation of the binding energetics and kinetics of the ligand-receptor interactions, therefore guiding the choice of the best candidate molecules for further development. The importance of considering the biological lipid bilayer environment in the MD simulations of membrane proteins is also discussed, using G-protein coupled receptors and ion channels as well as the drug-metabolizing cytochrome P450 enzymes as relevant examples. Lastly, we discuss the emerging role of MD simulations in facilitating the pharmaceutical formulation development of drugs and candidate drugs. Specifically, we look at how MD can be used in studying the crystalline and amorphous solids, the stability of amorphous drug or drug-polymer formulations, and drug solubility. Moreover, since nanoparticle drug formulations are of great interest in the field of drug delivery research, different applications of nano-particle simulations are also briefly summarized using multiple recent studies as examples. In the future, the role of MD simulations in facilitating the drug development process is likely to grow substantially with the increasing computer power and advancements in the development of force fields and enhanced MD methodologies.

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Section: Interactions With Viruses and Biomacromoleculesmentioning

confidence: 99%

Section: Interactions With Viruses and Biomacromoleculesmentioning

confidence: 99%

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

et al. 2020

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“…We also identify that the peptide is forming contact primarily via the carbonyl O atom of 1H, the side chain carboxyl oxygens of 4D and 5D and the terminal carboxyl oxygen of the 6D residues. However, there are some ligands (id: 12,26,33,34,35,40) which form strong binding over the entire last 500 ns of the trajectory, possible by forming contacts with multiple residues at the same time (representative cases are in Figure S6a,b) while some of the ligands (3, 21, 56) (Figure S6c,d) form transient weaker binding patch by showing back and forth motion towards peptide spanning a broad distance between 3 to 20 Å over simulation. Next, we probe inter-ligand fluctuations of the ligands belonging to the binding patch for the peptide.…”

Section: H(mentioning

confidence: 99%

“…In addition, the role of protonation of side chain arginine moieties on the adsorption of poly-arginine to silver NP as a function of pH has been investigated computationally [ 31 ]. Details of the interaction between amyloid β fibrils gold nanoparticles functionalized with ligands with different terminal groups [ 32 , 33 , 34 ] have been disclosed through MD simulation. Multiscale MD simulations [ 35 , 36 ] have been applied to unravel protein conformation and driving forces in protein–corona complexes formation.…”

Section: Introductionmentioning

confidence: 99%

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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“…The amount of surface charge strongly depends on the pH of the environment 8,9 and is controlled by the chemical equilibrium between hydronium ions and the functional groups. This process is known as charge regulation (CR) [10][11][12][13][14][15][16] . The concept of charge regulation was first described by Linderstrøm-Lang [17][18][19] and studied theoretically by Ninham and Parsegian.…”

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confidence: 99%

Charge Regulation of Colloidal Particles: Theory and Simulations

et al. 2019

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To explore charge regulation (CR) in physicochemical and biophysical systems, we present a model of colloidal particles with sticky adsorption sites which account for the formation of covalent bonds between the hydronium ions and the surface functional groups. Using this model and Monte Carlo simulations, we find that the standard Ninham and Parsegian (NP) theory of CR leads to results which deviate significantly from computer simulations. The problem of NP approach is traced back to the use of bulk equilibrium constant to account for surface chemical reactions. To resolve this difficulty we present a new theory of CR. The fundamental ingredient of the new approach is the sticky length, which is non-trivially related with the bulk equilibrium constant. The theory is found to be in excellent agreement with computer simulations, without any adjustable parameters. As an application of the theory we calculate the effective charge of colloidal particles containing carboxyl groups, as a function of pH and salt concentration.Electrostatic interactions play a fundamental role in physics, chemistry, and biology. The long-range nature of the Coulomb force, however, makes it very difficult to study theoretically 1 . In aqueous systems ions are usually hydrated by water molecules. On the other hand, acids lose proton, which associates with the water molecule forming a hydronium ion 2 . There are many reactions that are controlled by pH, and the acid-base equilibrium directly influences the functionality of biomolecules. Although pH can be easily tuned in experiments, it is much more difficult to account for the chemical equilibrium in theoretical and simulation studies 3 .Colloidal particles often have organic functional groups on their surfaces. In aqueous systems these groups dissociate, loosing a proton, resulting in a colloidal surface charge 4-7 . The amount of surface charge strongly depends on the pH of the environment 8,9 and is controlled by the chemical equilibrium between hydronium ions and the functional groups. This process is known as charge regulation (CR) 10-16 . The concept of charge regulation was first described by Linderstrøm-Lang 17-19 and studied theoretically by Ninham and Parsegian. 20 . CR is of fundamental importance in colloidal science 10,21-32 and biophysics 33-39 . It has been applied to explore the stability of electrical double layers 9,40-45 and is of great technological importance in fields as diverse as mineral preparation, agriculture, ceramics, and surface coating 46 .Consider a weak acid HA in equilibrium with bulk water, HA+H 2 O ⇄ H 3 O + +A -. For dilute solutions the concentration of all species is controlled by the law of mass action, K eq = c HA /c A -c H +,where K eq is the equilibrium constant and c indicates the concentration of each specie. Ninham and Parsegian (NP) supposed that the same equilibrium relation will hold for the reactive (acidic) sites on the colloidal surface with the local concentration of hydronium determined by the Boltzmann distribution, c surfq is the proto...

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Computational screening of nanoparticles coupling to Aβ40 peptides and fibrils

Cited by 11 publications

References 39 publications

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

Molecular Dynamics Simulations of a Catalytic Multivalent Peptide–Nanoparticle Complex

Charge Regulation of Colloidal Particles: Theory and Simulations

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