Free-Energy Analysis of Peptide Binding in Lipid Membrane Using All-Atom Molecular Dynamics Simulation Combined with Theory of Solutions

Mizuguchi, Tomoko; Matubayasi, Nobuyuki

doi:10.1021/acs.jpcb.7b08241

Cited by 22 publications

(14 citation statements)

References 112 publications

(179 reference statements)

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“…Amphiphilic peptides could behave differently because amphiphilic molecules such as cholesterol and other lipids follow a different translocation path, with the inserted state being parallel to the membrane (24,25). Nevertheless, two recent studies on translocation of a few specific AMPs suggest that the path could be similar to transmembrane helices (26,27).…”

Section: Introductionmentioning

confidence: 99%

Optimal Hydrophobicity and Reorientation of Amphiphilic Peptides Translocating through Membrane

Kabelka

Vácha

2018

Biophysical Journal

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Cell-penetrating and some antimicrobial peptides can translocate across lipid bilayers without disrupting the membrane structure. However, the molecular properties required for efficient translocation are not fully understood. We employed the Metropolis Monte Carlo method together with coarse-grained models to systematically investigate free-energy landscapes associated with the translocation of secondary amphiphilic peptides. We studied α-helical peptides with different length, amphiphilicity, and distribution of hydrophobic content and found a common translocation path consisting of adsorption, tilting, and insertion. In the adsorbed state, the peptides are parallel to the membrane plane, whereas, in the inserted state, the peptides are perpendicular to the membrane. Our simulations demonstrate that, for all tested peptides, there is an optimal ratio of hydrophilic/hydrophobic content at which the peptides cross the membrane the easiest. Moreover, we show that the hydrophobicity of peptide termini has an important effect on the translocation barrier. These results provide general guidance to optimize peptides for use as carriers of molecular cargos or as therapeutics themselves.

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Section: Introductionmentioning

confidence: 99%

Optimal Hydrophobicity and Reorientation of Amphiphilic Peptides Translocating through Membrane

Kabelka

Vácha

2018

Biophysical Journal

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“…f(ϵ i ) describes the effect of solvent reorganization due to the introduction of the solute, and the excluded-volume component ∆ν excl can be introduced by restricting the domain of integration in the third term of Eq. 22 to ϵ i >ϵ c as [86][87][88][90][91][92][93]…”

Section: Resultsmentioning

confidence: 99%

“…It is demonstrated quantitatively that urea and DMSO inhibit the aggregation since these cosolvents stabilize the monomer more strongly than the aggregates. pure-water solvent but also in more complex environments involving cosolvent or lipid membrane, that can be beyond the reach of exact free-energy methods or integral equation theories [30,81,86,[90][91][92][93][97][98][99][100][101][102]. The method of energy representation is approximate in practical applications, while it has been observed that the error from the approximation in the free-energy functional is not larger than the error from the use of force field [80,84,85].…”

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confidence: 99%

Energetics of cosolvent effect on peptide aggregation

Matubayasi

Masutani

2019

BIOPHYSICS

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The cosolvent effect on the equilibrium of peptide aggregation is reviewed from the energetic perspective. It is shown that the excess chemical potential is stationary against the variation of the distribution function for the configuration of a flexible solute species and that the derivative of the excess chemical potential with respect to the cosolvent concentration is determined by the corresponding derivative of the solvation free energy averaged over the solute configurations. The effect of a cosolvent at low concentrations on a chemical equilibrium can then be addressed in terms of the difference in the solvation free energy between pure-water solvent and the mixed solvent with the cosolvent, and illustrative analyses with all-atom model are presented for the aggregation of an 11-residue peptide by employing the energy-representation method to compute the solvation free energy. The solvation becomes more favorable with addition of the urea or DMSO cosolvent, and the extent of stabilization is smaller for larger aggregate. This implies that these cosolvents inhibit the formation of an aggregate, and the roles of such interaction components as the electrostatic, van der Waals, and excluded-volume are discussed.Protein or peptide can be harmful upon formation of aggregate [1][2][3][4]. It is considered that such amyloidoses as Alzheimer's, Parkinson's, and prion diseases are caused by the amyloid aggregation, and the formation of inclusion body is an impeding factor for massive expression in the field of protein engineering. The extent of aggregate formation of a peptide is determined by the interactions among the peptides forming the aggregate and those between the peptides and the surrounding solvent. In fact, the potential function is fixed for the interactions within the peptide aggregate when the peptide species is identified, whereas it can be tuned for the interactions with the surrounding environment. A common scheme for treating a peptide aggregate is thus to control the solvent environment with cosolvent [5-10], and since the cosolvent interacts with the peptide in a different manner from water, the interactions among the peptide, cosolvent, and water needs to be elucidated at the molecular level toward rational design of a cosolvent.The aggregation mechanism of peptide has been investigated both theoretically and experimentally . Molecular dynamics (MD) simulation has proven to be useful to address atomic-level processes, in particular, and the peptidepeptide and peptide-solvent interactions were analyzed to reveal the driving force of aggregate formation [12,14,16,[18][19][20][21][22][23][24]30]. In the context of statistical thermodynamics, the extent of peptide aggregation is described by the equilibrium constant of aggregation. It is determined by the balance of the The cosolvent effect on peptide aggregation is addressed with all-atom molecular dynamics simulation and freeenergy calculation. It is shown from the variational principle that the stability of a flexible solute species is modulated ...

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“…During the last twenty years, the development of molecular simulation (MS) technology has exhibited significant progress, especially since the 2013 Nobel Prize in Chemistry was awarded (Nie et al, 2018). To date, MS technology includes homology modelling (Nascimento et al, 2018), molecular docking (Arthur et al, 2018) and molecular dynamics simulation (Zhang et al, 2018), and combines free energy calculation (Mizuguchi & Matubayasi, 2018). Among these methods, molecular docking is the most widely used one in molecular modelling research.…”

Section: Introductionmentioning

confidence: 99%

Recent developments in molecular docking technology applied in food science: a review

Tao

Huang

Wang

et al. 2019

Int J of Food Sci Tech

139

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Molecular docking is a theoretical simulation method based on bioinformatics, which studies the interaction between molecules (such as ligands and receptors), and predicts their binding modes and affinity via a computer platform. This technology acts as a promising mean in medicinal chemistry such as structurebased rational drug design, which is accepted by researchers in the scientific community. During recent years, various fundamental studies involving biomolecular interaction in the food matrix have gradually emerged. The remarkable advantages of molecular docking such as predicting experiments are attracting increasing attention for its application potential in various fields. This review presents the theory and software development of molecular docking, and emphasises its application in the field of food science, including nutritional components and food safety. Moreover, the operational mechanisms of molecular docking are further summarised in this review.

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Free-Energy Analysis of Peptide Binding in Lipid Membrane Using All-Atom Molecular Dynamics Simulation Combined with Theory of Solutions

Cited by 22 publications

References 112 publications

Optimal Hydrophobicity and Reorientation of Amphiphilic Peptides Translocating through Membrane

Optimal Hydrophobicity and Reorientation of Amphiphilic Peptides Translocating through Membrane

Energetics of cosolvent effect on peptide aggregation

Recent developments in molecular docking technology applied in food science: a review

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