Mai Suan Li

Institut Universitaire de France, Lutetia Parisorum, Île-de-France, France

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Publications (113)323.21 Total impact

  • Pham Dinh Quoc Huy, Mai Suan Li
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    ABSTRACT: Binding affinity of fullerenes C20, C36, C60, C70 and C84 for amyloid beta fibrils is studied by docking and all-atom molecular dynamics simulations with the Amber force field and water model TIP3P. Using the molecular mechanic-Poisson Boltzmann surface area method one can demonstrate that the binding free energy linearly decreases with the number of carbon atoms of fullerene, i.e. the larger is the fullerene size, the higher is the binding affinity. Overall, fullerenes bind to Aβ9-40 fibrils stronger than to Aβ17-42. The number of water molecules trapped in the interior of 12Aβ9-40 fibrils was found to be lower than inside pentamer 5Aβ17-42. C60 destroys Aβ17-42 fibril structure to a greater extent compared to other fullerenes. Our study revealed that the van der Waals interaction dominates over the electrostatic interaction and non-polar residues of amyloid beta peptides play the significant role in interaction with fullerenes providing novel insight into the development of drug candidates against Alzheimer's disease.
    Physical Chemistry Chemical Physics 08/2014; · 4.20 Impact Factor
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    ABSTRACT: Recent experiments have shown that the Taiwan mutation (D7H) slows down the fibril formation of amyloid peptides Abeta40 and Abeta42. Motivated by this finding we have studied the influence of D7H mutation on structures of Abeta peptide monomers using the replica exchange molecular dynamics simulations with OPLS force field and implicit water model. Our study reveals that the mechanism behind modulation of aggregation rates is associated with decrease of beta-content and dynamics of the salt bridge D23-K28. Estimating the bending free energy of this salt bridge we have found that, in agreement with the experiments, the fibril formation rate of both peptides Abeta40 and Abeta42 is reduced about two times by mutation.
    The journal of physical chemistry. B. 07/2014;
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    ABSTRACT: The self-assembly of the amyloid beta (Abeta) peptides into senile plaques is the hallmark of Alzheimer's disease. Recent experiments have shown that the English familial disease mutation (H6R) speeds up the fibril formation process of alloforms Abeta40 and Abeta42 peptides altering their toxicity to cells. We used all-atom molecular dynamics simulations at microsecond-time scales with the OPLS-AA force field and TIP3P explicit water model to study the structural dynamics of the monomer and dimer of H6R sequences of both peptides. The reason behind the self-assembly acceleration is common that upon mutation the net charge is reduced leading to the weaker repulsive interaction between chains that facilitates the peptide association. However, we can show that the acceleration mechanisms are different for different peptides: the rate of fibril formation of Abeta42 increases due to the increase of beta-structure at the C-terminal in both monomer and dimer, while the enhancement of stability of the salt bridge Asp23-Lys28 plays the key role for Abeta40. Overall, our study provides a detailed atomistic picture of the H6R-mediated conformational changes that are consistent with the experimental findings and highlights the important role of the N-terminal in Abeta peptide aggregation.
    ACS Chemical Neuroscience 06/2014; · 3.87 Impact Factor
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    ABSTRACT: Stationary Josephson currentIc in symmetric and non-symmetric junctions involving d-wave superconductors with charge density waves (CDWs) was calculated. It was found that, if CDWs are weak or absent, there exists an approximate proportionality betweenIc and the product of superconducting order parameters in the electrodes (the lawof corresponding states) for several factors affecting those quantities, such as the temperature,T, or one of the parameters characterizing the combined CDW superconducting phase (the degree of the Fermi surface dielectric gapping and the ratio between the parent superconducting and CDW order parameters). Otherwise, the dependencesIc(T) were shown to deviate from those in the absence of CDWs, and the relevant corresponding-state dependences from linearity, the deviations being especially strong at certain rotation angles of crystalline electodes with respect to the junction plane. Hence, making use of specially designed experimental setups and analyzing theIc(T) and correspondingstate dependences, the existence of CDWs in cuprates and other non-conventional superconductors can be detected.
    The European Physical Journal B 05/2014; 87(5):115. · 1.28 Impact Factor
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    ABSTRACT: Amyloid oligomers and plaques are composed of multiple chemically identical proteins. Therefore, one of the first fundamental problems in the characterization of structures from simulations is the treatment of the degeneracy, i.e., the permutation of the molecules. Second, the intramolecular and intermolecular degrees of freedom of the various molecules must be taken into account. Currently, the well-known dihedral principal component analysis method only considers the intramolecular degrees of freedom, and other methods employing collective variables can only describe intermolecular degrees of freedom at the global level. With this in mind, we propose a general method that identifies all the structures accurately. The basis idea is that the intramolecular and intermolecular states are described in terms of combinations of single-molecule and double-molecule states, respectively, and the overall structures of oligomers are the product basis of the intramolecular and intermolecular states. This way, the degeneracy is automatically avoided. The method is illustrated on the conformational ensemble of the tetramer of the Alzheimer's peptide Aβ9-40, resulting from two atomistic molecular dynamics simulations in explicit solvent, each of 200 ns, starting from two distinct structures.
    The Journal of Chemical Physics 03/2014; 140(9):094105. · 3.12 Impact Factor
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    ABSTRACT: The influence of water models SPC, SPC/E, TIP3P, and TIP4P on ligand binding affinity is examined by calculating the binding free energy ΔG bind of oseltamivir carboxylate (Tamiflu) to the wild type of glycoprotein neuraminidase from the pandemic A/H5N1 virus. ΔG bind is estimated by the Molecular Mechanic-Poisson Boltzmann Surface Area method and all-atom simulations with different combinations of these aqueous models and four force fields AMBER99SB, CHARMM27, GROMOS96 43a1, and OPLS-AA/L. It is shown that there is no correlation between the binding free energy and the water density in the binding pocket in CHARMM. However, for three remaining force fields ΔG bind decays with increase of water density. SPC/E provides the lowest binding free energy for any force field, while the water effect is the most pronounced in CHARMM. In agreement with the popular GROMACS recommendation, the binding score obtained by combinations of AMBER-TIP3P, OPLS-TIP4P, and GROMOS-SPC is the most relevant to the experiments. For wild-type neuraminidase we have found that SPC is more suitable for CHARMM than TIP3P recommended by GROMACS for studying ligand binding. However, our study for three of its mutants reveals that TIP3P is presumably the best choice for CHARMM.
    The Scientific World Journal 01/2014; 2014:536084. · 1.73 Impact Factor
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    ABSTRACT: Recent experiments have shown that the mutation Tottori (D7N) alters the toxicity, assembly and rate of fibril formation of the wild type (WT) amyloid beta (Aβ) Aβ40 and Aβ42 peptides. We used all-atom molecular dynamics simulations in explicit solvent of the monomer and dimer of both alloforms with their WT and D7N sequences. The monomer simulations starting from a random coil and totaling 3 μs show that the D7N mutation changes the fold and the network of salt bridges in both alloforms. The dimer simulations starting from the amyloid fibrillar states and totaling 4.4 μs also reveal noticeable changes in terms of secondary structure, salt bridge, and topology. Overall, this study provides physical insights into the enhanced rate of fibril formation upon D7N mutation and an atomic picture of the D7N-mediated conformational change on Aβ40 and Aβ42 peptides.
    ACS Chemical Neuroscience 09/2013; · 3.87 Impact Factor
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    Dataset: jcp supp
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    Dataset: jcp supp
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    ABSTRACT: We discuss the use of a structure based Cα-Go model and Langevin dynamics to study in detail the mechanical properties and unfolding pathway of the titin I27 domain. We show that a simple Go-model does detect correctly the origin of the mechanical stability of this domain. The unfolding free energy landscape parameters xu and ΔG(‡), extracted from dependencies of unfolding forces on pulling speeds, are found to agree reasonably well with experiments. We predict that above v = 10(4) nm/s the additional force-induced intermediate state is populated at an end-to-end extension of about 75 A. The force-induced switch in the unfolding pathway occurs at the critical pulling speed vcrit ≈ 10(6)-10(7) nm/s. We argue that this critical pulling speed is an upper limit of the interval where Bell's theory works. However, our results suggest that the Go-model fails to reproduce the experimentally observed mechanical unfolding pathway properly, yielding an incomplete picture of the free energy landscape. Surprisingly, the experimentally observed intermediate state with the A strand detached is not populated in Go-model simulations over a wide range of pulling speeds. The discrepancy between simulation and experiment is clearly seen from the early stage of the unfolding process which shows the limitation of the Go model in reproducing unfolding pathways and deciphering the complete picture of the free energy landscape.
    The Journal of Chemical Physics 08/2013; 139(6):065103. · 3.12 Impact Factor
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    ABSTRACT: The tunnel conductance G(V) for break junctions made of single-crystal as-grown Bi2Sr2CaCu2O8+δ samples with Tc≈86–89 K were measured and clear-cut dip-hump structures (DHSs) were found in the range 80–120 mV of the bias voltage V. A theory of tunneling in symmetrical junctions between inhomogeneous charge-density-wave (CDW) superconductors, considered in the framework of the s-pairing model, has been developed. CDWs have been shown to be responsible for the appearance of the DHS in the tunnel current-voltage characteristics and properly describe the experimental results.
    Physical Review B 06/2013; 76(18). · 3.66 Impact Factor
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    ABSTRACT: We have developed the lattice model for describing polypeptide chains in the presence of crowders. The influence of crowding confinement on the fibrillation kinetics of polypeptide chains is studied using this model. We observed the non-trivial behavior of the fibril formation time τfib that it decreases with the concentration of crowders if crowder sizes are large enough, but the growth is observed for crowders of small sizes. This allows us to explain the recent experimental observation on the dual effect of crowding particles on fibril growth of proteins that for a fixed crowder concentration the fibrillation kinetics is fastest at intermediate values of total surface of crowders. It becomes slow at either small or large coverages of cosolutes. It is shown that due to competition between the energetics and entropic effects, the dependence of τfib on the size of confined space is described by a parabolic function.
    The Journal of Chemical Physics 05/2013; 138(18):185101. · 3.12 Impact Factor
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    ABSTRACT: The theory of the stationary Josephson tunnel current Ic was devised for junctions involving uperconductors partially gapped by biaxial or unidirectional charge density waves (CDWs) and possessing a superconducting order parameter of d-wave symmetry. Specific calculations were carried out for symmetric junctions between two identical CDW superconducting electrodes and nonsymmetric ones composed of a CDW superconductor and a conventional isotropic s-wave superconductor. Two kinds of superconducting pairing symmetries were studied, namely, that appropriate to cuprates (dx2−y2 ) and the dxy one. The corresponding calculations were also carried out for the extended s-wave symmetry of the superconducting order parameter. Allowances were made for the directionality of tunneling. In all the cases studied, the dependences of Ic on the angle γ between the chosen crystal direction and the normal to the junction plane were found to be significantly influenced by CDWs. It was shown in particular that the d-wave driven periodicity of Ic(γ ) in the CDW-free case is transformed into double-period beatings depending on the parameters of the system. The results of calculations testify that the orientation-dependent patterns Ic(γ ) measured for CDW superconductors allow the CDW configuration (unidirectional or checkerboard) and the symmetry of superconducting order parameter to be determined. The predicted effects can be used to indirectly reveal CDWs in underdoped cuprates where pseudogaps are observed. The break-junction technique is an appropriate tool for this purpose.
    Physical Review B 03/2013; 87(10):104503. · 3.66 Impact Factor
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    ABSTRACT: While amyloid-related diseases are at the center of intense research efforts, no real cure is currently being directed toward treating the diseases. The experimental and computational techniques were used to study the ability of glyco-acridines to prevent lysozyme amyloid fibrillization in vitro. Fluorescence spectroscopy and transmission electron microscopy have shown that glyco-acridines inhibit amyloid aggregation of lysozyme; the inhibition efficiency characterized by the half-maximal inhibition concentration IC50 was affected by derivative structure and concentration. We have investigated relationship between the binding affinity and the inhibition activity of the compounds. The good correlation was reached within the framework of the semiempirical quantum PM6-DH+ method pointing to importance of quantum effects in binding of glyco-acridine derivatives to lysozyme. The role of linkers may be understood within the Valence Bond theory. Our data provide a basis for the development of novel small molecules effective in therapy of amyloid-related diseases.
    Biomacromolecules 02/2013; · 5.37 Impact Factor
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    ABSTRACT: BACKGROUND: Aggregation of amyloid-beta (Aβ) has been proposed as the main cause of Alzheimer's disease (AD). Vitamin K deficiency has been linked to the pathogenesis of AD. Therefore, 15 synthesized vitamin K3 (VK3) analogues were studied for their anti-amyloidogenic activity. METHODS: Biological and spectroscopic assays were used to characterize the effect of VK3 analogues on amyloidogenic properties of Aβ, such as aggregation, free radical formation, and cell viability. Molecular dynamics simulation was used to calculate the binding affinity and mode of VK3 analogue binding to Aβ. RESULTS: Both numerical and experimental results showed that several VK3 analogues, including VK3-6, VK3-8, VK3-9, VK3-10, and VK3-224 could effectively inhibit Aβ aggregation and conformational conversion. The calculated inhibition constants were in the μM range for VK3-10, VK3-6, and VK3-9 which was similar to the IC(50) of curcumin. Cell viability assays indicated that VK3-9 could effectively reduce free radicals and had a protective effect on cytotoxicity induced by Aβ. CONCLUSIONS: The results clearly demonstrated that VK3 analogues could effectively inhibit Aβ aggregation and protect cells against Aβ induced toxicity. Modified VK3 analogues can possibly be developed as effective anti-amyloidogenic drugs for the treatment of AD. GENERAL SIGNIFICANCE: VK3 analogues effectively inhibit Aβ aggregation and are highly potent as anti-amyloidogenic drugs for therapeutic treatment of AD.
    Biochimica et Biophysica Acta 01/2013; · 4.66 Impact Factor
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    ABSTRACT: By the virtual screening method we have screened out Dihydrochalcone as a top-lead for the Alzheimer's disease using the database of about 32364 natural compounds. The binding affinity of this ligand to amyloid beta (A[Formula: see text]) fibril has been thoroughly studied by computer simulation and experiment. Using the Thioflavin T (ThT) assay we have obtained the inhibition constant IC50 [Formula: see text]M. This result is in good agreement with the estimation of the binding free energy obtained by the molecular mechanic-Poisson Boltzmann surface area method and all-atom simulation with the force field CHARMM 27 and water model TIP3P. Cell viability assays indicated that Dihydrochalcone could effectively reduce the cytotoxicity induced by A[Formula: see text]. Thus, both in silico and in vitro studies show that Dihydrochalcone is a potential drug for the Alzheimers disease.
    PLoS ONE 01/2013; 8(11):e79151. · 3.53 Impact Factor
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    ABSTRACT: Dependences of the stationary Josephson current in symmetric and nonsymmetric tunnel junctions involving d-wave superconductors with charge density waves (CDWs) on the system parameters were calculated. Both the checkerboard and unidirectional CDW patterns were studied. The directionality of tunneling was taken into account. It was shown that CDWs can drastically influence the Josephson current, the changes being more significant in underdoped compositions.
    Metallofizika i noveĭshie tekhnologii 01/2013; · 0.11 Impact Factor
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    ABSTRACT: Recently it has been proposed a model for fibrils of human insulin in which the fibril growth proceeds via stacking LVEALYL (fragment 11-17 from chain B of insulin) into pairs of tightly interdigitated [Formula: see text]-sheets. The experiments have also shown that LVEALYL has high propensity to self-assembly and binding to insulin. This necessitates study of oligomerization of LVEALYL and its binding affinity to full-length insulin. Using the all-atom simulations with Gromos96 43a1 force field and explicit water it is shown that LVEALYL can aggregate. Theoretical estimation of the binding free energy of LVEALYL to insulin by the molecular mechanic Poisson-Boltzmann surface area method reveals its strong binding affinity to chain B, implying that, in agreement with the experiments, LVEALYL can affect insulin aggregation via binding mechanism. We predict that, similar to LVEALYL, peptide RGFFYT (fragment B22-27) can self-assemble and bind to insulin modulating its fibril growth process. The binding affinity of RGFFYT is shown to be comparable with that of LVEALYL.
    PLoS ONE 01/2013; 8(6):e65358. · 3.53 Impact Factor
  • Mai Suan Li, Binh Khanh Mai
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    ABSTRACT: About 15 years ago, the steered molecular dynamics (SMD) was used to probe binding of ligand to biomolecule surfaces but in terms of drug design this approach has only recently attached attention of researchers. The main idea of using SMD to screen out leads is based on the hypothesis that the larger is the force needed to unbind a ligand from a receptor the higher its binding affinity. Thus, instead of binding free energy, the rupture force defined as the maximum on the force-time/displacement profile, is used as a score function. In this mini-review, we discuss basic concepts behind the experimental technique atomic force microscopy as well as SMD. Experimental and theoretical works on the application of SMD to the drug design problem are covered. Accumulated evidences show that SMD is as accurate as the molecular mechanics-Poisson-Boltzmann surface area method in predicting ligand binding affinity but the former is computationally much more efficient. The high correlation level between theoretically determined rupture forces and experimental data on binding energies implies that SMD is a promising tool for drug design. Our special attention is drawn to recent studies on inhibitors of influenza viruses.
    Current Bioinformatics 12/2012; 7(4):342-351. · 2.02 Impact Factor

Publication Stats

1k Citations
323.21 Total Impact Points

Institutions

  • 2014
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • National Tsing Hua University
      Hsin-chu-hsien, Taiwan, Taiwan
  • 1994–2013
    • University of Warsaw
      • Institute of Theoretical Physics
      Warszawa, Masovian Voivodeship, Poland
  • 1990–2013
    • Polish Academy of Sciences
      • Institute of Physics
      Warsaw, Masovian Voivodeship, Poland
  • 2009–2012
    • Academia Sinica
      • Institute of Physics
      T’ai-pei, Taipei, Taiwan
  • 2011
    • Hiroshima University
      • Graduate School of Integrated Arts and Sciences
      Hiroshima-shi, Hiroshima-ken, Japan
  • 2005–2011
    • Goethe-Universität Frankfurt am Main
      • Institut für Physikalische und Theoretische Chemie
      Frankfurt am Main, Hesse, Germany
  • 2010
    • Visva Bharati University
      • Department of Chemistry
      Bolpur, Bengal, India