@article {2020|2117, title = {Aggregation of disease-related peptides.}, journal = {Prog Mol Biol Transl Sci}, volume = {170}, year = {2020}, month = {2020}, pages = {435-460}, abstract = {

Protein misfolding and aggregation of amyloid proteins is the fundamental cause of more than 20 diseases. Molecular mechanisms of the self-assembly and the formation of the toxic aggregates are still elusive. Computer simulations have been intensively used to study the aggregation of amyloid peptides of various amino acid lengths related to neurodegenerative diseases. We review atomistic and coarse-grained simulations of short amyloid peptides aimed at determining their transient oligomeric structures and the early and late aggregation steps.

}, issn = {1878-0814}, doi = {10.1016/bs.pmbts.2019.12.002}, author = {Phuong Hoang Nguyen and Sterpone, Fabio and Philippe Derreumaux} } @article {2020|2126, title = {Impact of A2T and D23N Mutations on Tetrameric Aβ42 Barrel within a Dipalmitoylphosphatidylcholine Lipid Bilayer Membrane by Replica Exchange Molecular Dynamics.}, journal = {J Phys Chem B}, volume = {124}, year = {2020}, month = {2020 Feb 20}, pages = {1175-1182}, abstract = {

In Alzheimer\&$\#$39;s disease (AD), many experimental and computational studies support the amyloid pore hypothesis of the Aβ42 peptide. We recently designed a β-barrel tetramer in a membrane-mimicking environment consistent with some low-resolution experimental data. In this earlier study, by using extensive replica exchange molecular dynamics simulations, we found that the wild-type (WT) Aβ42 peptides have a high propensity to form β-barrels, while the WT Aβ40 peptides do not. In this work, we have investigated the effect of mutations D23N and A2T on the Aβ42 barrel tetramer by using the same enhanced conformational sampling technique. It is known that the D23N mutation leads to early onset AD, while the A2T mutation protects from AD. This computational study in a dipalmitoylphosphatidylcholine (DPPC) lipid bilayer membrane shows that the WT sequence and its A2T variant have similar β-barrel populations and the three-dimensional model is slightly destabilized for D23N compared to its WT sequence. These extensive modeling calculations indicate that the lower and higher induced toxicity of these two mutations in AD cannot be correlated to their β-barrel tetramer stabilities in a DPPC lipid bilayer membrane.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.9b11881}, author = {Ngo, Son Tung and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2020|2116, title = {Stability of Aβ11-40 Trimers with Parallel and Antiparallel β-Sheet Organizations in a Membrane-Mimicking Environment by Replica Exchange Molecular Dynamics Simulation}, journal = {The Journal of Physical Chemistry B}, year = {2020}, author = {Ngo, Son Tung and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2020|2131, title = {Tau R3-R4 Domain Dimer of the Wild Type and Phosphorylated Ser356 Sequences. I. In Solution by Atomistic Simulations.}, journal = {J Phys Chem B}, year = {2020}, month = {2020 Mar 27}, abstract = {

In Alzheimer\&$\#$39;s disease, neurofibrillary lesions correlate with cognitive deficits and consist of inclusions of tau protein with cross-β structure. A stable dimeric form of soluble tau has been evidenced in the cells, but its high-resolution structure is missing in solution. We know, however, that cryo-electron microscopy (c-EM) of full-length tau in the brain of an individual with AD displays a core of eight β-sheets with a C-shaped architecture spanning the R3-R4 repeat domain, while the rest of the protein is very flexible. To address the conformational ensemble of the dimer, we performed atomistic replica exchange molecular dynamics simulations on the tau R3-R4 domain starting from the c-EM configuration. We find that the wild type tau R3-R4 dimer explores elongated, U-shaped, V-shaped and globular forms rather than the C-shape. Phosphorylation of Ser356, pSer356, is known to block the interaction between the tau protein and the amyloid-β42 peptide. Standard molecular dynamics simulations of this phosphorylated sequence for a total of 5 microseconds compared to its wild type counterpart show a modulation of the population of β-helices and accessible topologies, and a decrease of intermediates near the fibril like conformers.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.0c00574}, author = {Philippe Derreumaux and Man, Viet Hoang and Wang, Junmei and Phuong Hoang Nguyen} } @article {2019|2109, title = {Amyloid-β (29{\textendash}42) Dimeric Conformations in Membranes Rich in Omega-3 and Omega-6 Polyunsaturated Fatty Acids}, journal = {The Journal of Physical Chemistry B}, volume = {123}, year = {2019}, pages = {2687{\textendash}2696}, author = {Lu, Yan and Shi, Xiao-Feng and Phuong Hoang Nguyen and Sterpone, Fabio and Salsbury Jr, Freddie R and Philippe Derreumaux} } @article {2019|2110, title = {Effects of all-atom molecular mechanics force fields on amyloid peptide assembly: the case of aβ16{\textendash}22 dimer}, journal = {Journal of chemical theory and computation}, volume = {15}, year = {2019}, pages = {1440{\textendash}1452}, author = {Man, Viet Hoang and He, Xibing and Philippe Derreumaux and Ji, Beihong and Xie, Xiang-Qun and Phuong Hoang Nguyen and Wang, Junmei} } @article {2019|2108, title = {Interaction mechanism between the focused ultrasound and lipid membrane at the molecular level}, journal = {The Journal of chemical physics}, volume = {150}, year = {2019}, pages = {215101}, author = {Man, Viet Hoang and Li, Mai Suan and Wang, Junmei and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2019|2107, title = {Nonequilibrium atomistic molecular dynamics simulation of tubular nanomotor propelled by bubble propulsion}, journal = {The Journal of chemical physics}, volume = {151}, year = {2019}, pages = {024103}, author = {Man, Viet Hoang and Li, Mai Suan and Wang, Junmei and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2019|2105, title = {Tetrameric Aβ40 and Aβ42 β-Barrel Structures by Extensive Atomistic Simulations. II. In Aqueous Solution.}, journal = {J Phys Chem B}, volume = {123}, year = {2019}, month = {2019 Aug 08}, pages = {6750-6756}, abstract = {

Alzheimer\&$\#$39;s disease (AD) is characterized by the accumulation of extracellular Aβ42 and Aβ40 oligomers and plaques. In a recent computational study, we found that the presence of the residues I41 and A42 increases significantly the propensity of Aβ to form a tetrameric β-barrel structure in a bilayer mimicking a neuronal membrane. In this work, we have determined the propensity of the two Aβ proteins to form tetrameric β-barrel structures in aqueous solution using four atomistic protein fields, that is, Amber99SB-ILDN/TIP3P, OPLS/TIP3P, CHARMM36m/TIP3P-modified, and Amber99SB/DISP. Extensive replica exchange molecular dynamics simulations make it clear that a β-barrel, made of two distinct β-hairpin motifs and an asymmetric arrangement of eight antiparallel β-strands with an inner pore diameter of 0.7 nm, exists transiently for Aβ42 peptide, but this is less the case for Aβ40 peptide, due to the change of the CHC-CHC and the Cter-Cter interfaces. This study has several implications in AD.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.9b05288}, author = {Phuong Hoang Nguyen and Campanera, Josep M and Ngo, Son Tung and Loquet, Antoine and Philippe Derreumaux} } @article {2019|2106, title = {Tetrameric Aβ40 and Aβ42 β-Barrel Structures by Extensive Atomistic Simulations. I. In a Bilayer Mimicking a Neuronal Membrane.}, journal = {J Phys Chem B}, volume = {123}, year = {2019}, month = {2019 May 02}, pages = {3643-3648}, abstract = {

The amyloid-β (Aβ) 42 oligomers are much more toxic than Aβ40 oligomers in Alzheimer\&$\#$39;s disease. Numerous experiments indicate that toxicity could involve the formation of pores in membranes, but experimental high-resolution structure determination of these pore-forming Aβ oligomers has been impeded by aggregate heterogeneity. Using extensive atomistic simulations, low-resolution data obtained in lipid bilayers, and other theoretical factors, we proposed atomic structures of Aβ40 and Aβ42 β-barrels in a bilayer mimicking a neuronal membrane. The 3D model, which consists of tetramer subunits, two distinct β-hairpin motifs and an asymmetric arrangement of eight antiparallel β-strands, is drastically destabilized for Aβ40 compared to its Aβ42 counterpart. Our computational modeling has several implications in Alzheimer\&$\#$39;s disease, sheds light on the amyloid pore hypothesis, and explains the higher deleterious property of Aβ42.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.9b01206}, author = {Phuong Hoang Nguyen and Campanera, Josep M and Ngo, Son Tung and Loquet, Antoine and Philippe Derreumaux} } @article {2018|2113, title = {Amyloid-β/drug interactions from computer simulations and cell-based assays}, journal = {Journal of Alzheimer{\textquoteright}s Disease}, volume = {64}, year = {2018}, pages = {S659{\textendash}S672}, author = {Phuong Hoang Nguyen and Del Castillo-Frias, Maria P and Berthoumieux, Olivia and Faller, Peter and Doig, Andrew J and Philippe Derreumaux} } @article {2018|2112, title = {Breaking down cellulose fibrils with a mid-infrared laser}, journal = {Cellulose}, volume = {25}, year = {2018}, pages = {5553{\textendash}5568}, author = {Domin, Dominik and Man, Viet Hoang and Van-Oanh, Nguyen-Thi and Wang, Junmei and Kawasaki, Takayasu and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2018|2111, title = {Molecular mechanism of the cell membrane pore formation induced by bubble stable cavitation}, journal = {The Journal of Physical Chemistry B}, volume = {123}, year = {2018}, pages = {71{\textendash}78}, author = {Man, Viet Hoang and Truong, Phan Minh and Li, Mai Suan and Wang, Junmei and Van-Oanh, Nguyen-Thi and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2018|2114, title = {Rayleigh-Plesset equation of the bubble stable cavitation in water: A nonequilibrium all-atom molecular dynamics simulation study}, journal = {The Journal of Chemical Physics}, volume = {148}, year = {2018}, pages = {094505}, author = {Man, Viet Hoang and Li, Mai Suan and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2017|2032, title = {Conformational Ensembles of the Wild-Type and S8C Aβ1-42 Dimers.}, journal = {J Phys Chem B}, volume = {121}, year = {2017}, month = {2017 Mar 23}, pages = {2434-2442}, abstract = {

We characterized the dimer of the amyloid-β wild-type (WT) peptide, Aβ, of 42 residues and its disulfide-bond-locked double mutant (S8C) by replica exchange molecular dynamics simulations. Aβ dimers are known to be the smallest toxic species in Alzheimer\&$\#$39;s disease, and the S8C mutant has been shown experimentally to form an exclusive homogeneous and neurotoxic dimer. Our 50 μs all-atom simulations reveal similar secondary structures and collision cross-sections but very different intramolecular and intermolecular conformations upon double S8C mutation. Both dimers are very dynamic with hundreds of free-energy minima that differ from the U-shape and S-shape conformations of the peptides in the fibrils. The only common structural feature, shared by both species with a probability of 4\% in WT and 12\% in S8C-S8C, is a three-stranded β-sheet spanning the 17-23, 29-36, and 39-41 residues, which does not exist in the Aβ40 WT dimers.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b00267}, author = {Man, Viet Hoang and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2017|2031, title = {High-Resolution Structures of the Amyloid-β 1-42 Dimers from the Comparison of Four Atomistic Force Fields.}, journal = {J Phys Chem B}, volume = {121}, year = {2017}, month = {2017 Jun 22}, pages = {5977-5987}, abstract = {

The dimer of the amyloid-β peptide Aβ of 42 residues is the smallest toxic species in Alzheimer\&$\#$39;s disease, but its equilibrium structures are unknown. Here we determined the equilibrium ensembles generated by the four atomistic OPLS-AA, CHARMM22*, AMBER99sb-ildn, and AMBERsb14 force fields with the TIP3P water model. On the basis of 144 μs replica exchange molecular dynamics simulations (with 750 ns per replica), we find that the four force fields lead to random coil ensembles with calculated cross-collision sections, hydrodynamics properties, and small-angle X-ray scattering profiles independent of the force field. There are, however, marked differences in secondary structure, with the AMBERsb14 and CHARMM22* ensembles overestimating the CD-derived helix content, and the OPLS-AA and AMBER99sb-ildn secondary structure contents in agreement with CD data. Also the intramolecular beta-hairpin content spanning residues 17-21 and 30-36 varies between 1.5\% and 13\%. Overall, there are significant differences in tertiary and quaternary conformations among all force fields, and the key finding, irrespective of the force field, is that the dimer is stabilized by nonspecific interactions, explaining therefore its possible transient binding to multiple cellular partners and, in part, its toxicity.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b04689}, author = {Man, Viet Hoang and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2017|2029, title = {Multi-scale simulations of biological systems using the OPEP coarse-grained model.}, journal = {Biochem Biophys Res Commun}, year = {2017}, month = {2017 Sep 14}, abstract = {

Biomolecules are complex machines that are optimized by evolution to properly fulfill or contribute to a variety of biochemical tasks in the cellular environment. Computer simulations based on quantum mechanics and atomistic force fields have been proven to be a powerful microscope for obtaining valuable insights into many biological, physical, and chemical processes. Many interesting phenomena involve, however, a time scale and a number of degrees of freedom, notably if crowding is considered, that cannot be explored at an atomistic resolution. To bridge the gap between reality and simulation, many different advanced computational techniques and coarse-grained (CG) models have been developed. Here, we report some applications of the CG OPEP protein model to amyloid fibril formation, the response of catch-bond proteins to two types of fluid flow, and interactive simulations to fold peptides with well-defined 3D structures or with intrinsic disorder.

}, issn = {1090-2104}, doi = {10.1016/j.bbrc.2017.08.165}, author = {Sterpone, Fabio and Doutreligne, S{\'e}bastien and Tran, Thanh Thuy and Melchionna, Simone and Marc Baaden and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2017|2030, title = {Why Is Research on Amyloid-β Failing to Give New Drugs for Alzheimer{\textquoteright}s Disease?}, journal = {ACS Chem Neurosci}, volume = {8}, year = {2017}, month = {2017 Jul 19}, pages = {1435-1437}, abstract = {

The two hallmarks of Alzheimer\&$\#$39;s disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure.

}, keywords = {Alzheimer Disease, Amyloid beta-Peptides, Animals, Drug Discovery, Humans, Neuroprotective Agents}, issn = {1948-7193}, doi = {10.1021/acschemneuro.7b00188}, author = {Doig, Andrew J and Del Castillo-Frias, Maria P and Berthoumieu, Olivia and Tarus, Bogdan and Nasica-Labouze, Jessica and Sterpone, Fabio and Phuong Hoang Nguyen and Hooper, Nigel M and Faller, Peter and Philippe Derreumaux} } @conference {2016|1606, title = {Alzheimer{\textquoteright}s Disease: Insights into Amyloid Fibril Formation from Lattice Monte Carlo Simulations}, booktitle = {Biophys. J.}, volume = {110}, number = {3, 1}, year = {2016}, note = {60th Annual Meeting of the Biophysical-Society, Los Angeles, CA, FEB 27-MAR 02, 2016}, month = {feb}, pages = {219A}, publisher = {Biophys Soc}, organization = {Biophys Soc}, issn = {0006-3495}, author = {Thanh-Thuy Tran and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2016|2115, title = {Aβ41 Aggregates More Like Aβ40 than Like Aβ42: In Silico and in Vitro Study}, journal = {The Journal of Physical Chemistry B}, volume = {120}, year = {2016}, pages = {7371{\textendash}7379}, author = {Nguyen, Hoang Linh and Thi Minh Thu, Tran and Truong, Phan Minh and Lan, Pham Dang and Man, Viet Hoang and Phuong Hoang Nguyen and Tu, Ly Anh and Chen, Yi-Cheng and Li, Mai Suan} } @article {2016|1656, title = {Coarse-grained and All-atom Simulations towards the Early and Late Steps of Amyloid Fibril Formation}, journal = {Isr. J. Chem.}, volume = {DOI: 10.1002/ijch.201600048.}, year = {2016}, author = {M. Chiricotto and Thanh-Thuy Tran and Phuong Hoang Nguyen and S. Melchionna and Fabio Sterpone and Philippe Derreumaux} } @article {2016|1712, title = {Dimerization Mechanism of Alzheimer A beta(40) Peptides: The High Content of Intrapeptide-Stabilized Conformations in A2V and A2T Heterozygous Dimers Retards Amyloid Fibril Formation}, journal = {J. Phys. Chem. B}, volume = {120}, number = {47}, year = {2016}, pages = {12111{\textendash}12126}, abstract = {Amyloid beta (A beta) oligomerization is associated with the origin and progression of Alzheimer{\textquoteright}s disease (AD). While the A2V mutation enhances aggregation kinetics and toxicity, mixtures of wild-type (WT) and A2V, and also WT and A2T, peptides retard fibril formation and protect against AD. In this study, we simulate the equilibrium ensemble of WT:A2T A beta(40) dimer by means of extensive atomistic replica exchange molecular dynamics and compare our results with previous equivalent simulations of A2V:A2V, WT:WT, and WT:A2V A beta(40) dimers for a total time scale of nearly 0.1 ms. Qualitative comparison of the resulting thermodynamic properties, such as the relative binding free energies, with the reported experimental kinetic and thermodynamic data affords us important insight into the conversion from slow-pathway to fast-pathway dimer conformations. The crucial reaction coordinate or driving force of such transformation turns out to be related to hydrophobic interpeptide interactions. Analysis of the equilibrium ensembles shows that the fast-pathway conformations contain interpeptide out-of-register antiparallel beta-sheet structures at short interpeptide distances. In contrast, the slow-pathway conformations are formed by the association of peptides at large interpeptide distances and high intrapeptide compactness, such as conformations containing intramolecular three-stranded beta-sheets which sharply distinguish fast (A2V:A2V and WT:WT) and slow (WT:A2T and WT:A2V) amyloid-forming sequences. Also, this analysis leads us to predict that a molecule stabilizing the intramolecular three-stranded beta-sheet or inhibiting the formation of an interpeptide beta-sheet spanning residues 17-20 and 31-37 would further reduce fibril formation and probably the cytotoxicity of A beta species.}, issn = {1520-6106}, doi = {10.1021/acs.jpcp.6b10722}, author = {Phuong Hoang Nguyen and Fabio Sterpone and Pouplana, Ramon and Philippe Derreumaux and Campanera, Josep M.} } @article {2016|1578, title = {Impact of the A2V Mutation on the Heterozygous and Homozygous A beta 1-40 Dimer Structures from Atomistic Simulations}, journal = {Acs Chem. Neurosci.}, volume = {7}, number = {6}, year = {2016}, month = {jun}, pages = {823{\textendash}832}, abstract = {The A2V mutation was reported to protect from Alzheimer{\textquoteright}s disease in its heterozygous form and cause an early Alzheimer{\textquoteright}s disease type dementia in its homozygous form. Experiments showed that the aggregation rate follows the order A2V > WT (wild-type) > A2V-WT. To understand the impact of this mutation, we carried out replica exchange molecular dynamics simulations of A beta 1-40 WT-A2V and A2V-A2V dimers and compared to the WT dimer. Our atomistic simulations reveal that the mean secondary structure remains constant, but there are substantial differences in the intramolecular and intermolecular conformations upon single and double A2V mutation. Upon single mutation, the intrinsic disorder is reduced, the intermolecular potential energies are reduced, the population of intramolecular three-stranded beta-sheets is increased, and the number of all a dimer topologies is decreased. Taken together, these results offer an explanation for the reduced aggregation rate of the A beta 1-40 A2V-WT peptides and the protective effect of A2V in heterozygotes.}, issn = {1948-7193}, doi = {10.1021/acschemneuro.6b00053}, author = {Phuong Hoang Nguyen and Fabio Sterpone and Campanera, Josep M. and Nasica-Labouze, Jessica and Philippe Derreumaux} } @article {2016|1703, title = {Lattice model for amyloid peptides: OPEP force field parametrization and applications to the nucleus size of Alzheimer{\textquoteright}s peptides}, journal = {J. Chem. Phys.}, volume = {144}, number = {20}, year = {2016}, month = {may}, abstract = {Coarse-grained protein lattice models approximate atomistic details and keep the essential interactions. They are, therefore, suitable for capturing generic features of protein folding and amyloid formation at low computational cost. As our aim is to study the critical nucleus sizes of two experimentally well-characterized peptide fragments A beta(16-22) and A beta(37-42) of the full length A beta(1-42) Alzheimer{\textquoteright}s peptide, it is important that simulations with the lattice model reproduce all-atom simulations. In this study, we present a comprehensive force field parameterization based on the OPEP (Optimized Potential for Efficient protein structure Prediction) force field for an on-lattice protein model, which incorporates explicitly the formation of hydrogen bonds and directions of side-chains. Our bottom-up approach starts with the determination of the best lattice force parameters for the A beta(16-22) dimer by fitting its equilibrium parallel and anti-parallel beta-sheet populations to all-atom simulation results. Surprisingly, the calibrated force field is transferable to the trimer of A beta(16-22) and the dimer and trimer of A beta(37-42). Encouraged by this finding, we characterized the free energy landscapes of the two decamers. The dominant structure of the A beta(16-22) decamer matches the microcrystal structure. Pushing the simulations for aggregates between 4-mer and 12-mer suggests a nucleus size for fibril formation of 10 chains. In contrast, the A beta(37-42) decamer is largely disordered with mixed by parallel and antiparallel chains, suggesting that the nucleus size is >10 peptides. Our refined force field coupled to this on-lattice model should provide useful insights into the critical nucleation number associated with neurodegenerative diseases. Published by AIP Publishing.}, issn = {0021-9606}, doi = {10.1063/1.4951739}, author = {Thanh-Thuy Tran and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2016|1703, title = {Nonequilibrium all-atom molecular dynamics simulation of the bubble cavitation and application to dissociate amyloid fibrils}, journal = {J. Chem. Phys.}, volume = {145}, number = {17}, year = {2016}, month = {nov}, abstract = {The cavitation of gas bubbles in liquids has been applied to different disciplines in life and natural sciences, and in technologies. To obtain an appropriate theoretical description of effects induced by the bubble cavitation, we develop an all-atom nonequilibrium molecular-dynamics simulation method to simulate bubbles undergoing harmonic oscillation in size. This allows us to understand the mechanism of the bubble cavitation-induced liquid shear stress on surrounding objects. The method is then employed to simulate an A beta fibril model in the presence of bubbles, and the results show that the bubble expansion and contraction exert water pressure on the fibril. This yields to the deceleration and acceleration of the fibril kinetic energy, facilitating the conformational transition between local free energy minima, and leading to the dissociation of the fibril. Our work, which is a proof-of-concept, may open a new, efficient way to dissociate amyloid fibrils using the bubble cavitation technique, and new venues to investigate the complex phenomena associated with amyloidogenesis. Published by AIP Publishing.}, issn = {0021-9606}, doi = {10.1063/1.4966263}, author = {Man Hoang Viet and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2016|1744, title = {Picosecond infrared laser-induced all-atom nonequilibrium molecular dynamics simulation of dissociation of viruses}, journal = {Phys. Chem. Chem. Phys.}, volume = {18}, number = {17}, year = {2016}, month = {may}, pages = {11951{\textendash}11958}, abstract = {Since the discovery of the plant pathogen tobacco mosaic virus as the first viral entity in the late 1800s, viruses traditionally have been mainly thought of as pathogens for disease-resistances. However, viruses have recently been exploited as nanoplatforms with applications in biomedicine and materials science. To this aim, a large majority of current methods and tools have been developed to improve the physical stability of viral particles, which may be critical to the extreme physical or chemical conditions that viruses may encounter during purification, fabrication processes, storage and use. However, considerably fewer studies are devoted to developing efficient methods to degrade or recycle such enhanced stability biomaterials. With this in mind, we carry out all-atom nonequilibriummolecular dynamics simulation, inspired by the recently developed mid-infrared free-electron laser pulse technology, to dissociate viruses. Adopting the poliovirus as a representative example, we find that the primary step in the dissociation process is due to the strong resonance between the amide I vibrational modes of the virus and the tuned laser frequencies. This process is determined by a balance between the formation and dissociation of the protein shell, reflecting the highly plasticity of the virus. Furthermore, our method should provide a feasible approach to simulate viruses, which is otherwise too expensive for conventional equilibrium all-atom simulations of such very large systems. Our work shows a proof of concept which may open a new, efficient way to cleave or to recycle virus-based materials, provide an extremely valuable tool for elucidating mechanical aspects of viruses, and may well play an important role in future fighting against virus-related diseases.}, issn = {1463-9076}, doi = {10.1039/c5cp07711g}, author = {Viet Hoang Man and Van-Oanh, Nguyen-Thi and Philippe Derreumaux and Li, Mai Suan and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2015|1634, title = {Amyloid beta Protein and Alzheimer{\textquoteright}s Disease: When Computer Simulations Complement Experimental Studies}, journal = {Chem. Rev.}, volume = {115}, number = {9}, year = {2015}, month = {may}, pages = {3518{\textendash}3563}, doi = {10.1021/cr500638n}, author = {Nasica-Labouze, Jessica and Phuong Hoang Nguyen and Fabio Sterpone and Berthoumieu, Olivia and Buchete, Nicolae-Viorel and Cote, Sebastien and De Simone, Alfonso and Doig, Andrew J. and Faller, Peter and Garcia, Angel and Laio, Alessandro and Li, Mai Suan and Melchionna, Simone and Mousseau, Normand and Mu, Yuguang and Paravastu, Anant and Pasquali, Samuela and Rosenman, David J. and Strodel, Birgit and Tarus, Bogdan and Viles, John H. and Zhang, Tong and Wang, Chunyu and Philippe Derreumaux} } @article {2015|1635, title = {Combined Experimental and Simulation Studies Suggest a Revised Mode of Action of the Anti-Alzheimer Disease Drug NQ-Trp}, journal = {Chemistry-a European Journal}, volume = {21}, number = {36}, year = {2015}, pages = {12657{\textendash}12666}, doi = {10.1002/chem.201500888}, author = {Berthoumieu, Olivia and Phuong Hoang Nguyen and del Castillo-Frias, Maria P. and Ferre, Sabrina and Tarus, Bogdan and Nasica-Labouze, Jessica and Noel, Sabrina and Saurel, Olivier and Rampon, Claire and Doig, Andrew J. and Philippe Derreumaux and Faller, Peter} } @article {2015|1704, title = {Communication: Multiple atomistic force fields in a single enhanced sampling simulation}, journal = {J. Chem. Phys.}, volume = {143}, number = {2}, year = {2015}, month = {jul}, pages = {021101}, doi = {10.1063/1.4926535}, author = {Man Hoang Viet and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2015|1768, title = {Communication: Multiple atomistic force fields in a single enhanced sampling simulation.}, journal = {The Journal of Chemical Physics}, volume = {143}, number = {2}, year = {2015}, month = {jul}, pages = {021101{\textendash}021101}, doi = {10.1063/1.4926535}, author = {Hoang Viet, Man and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2015|1713, title = {Folding Atomistic Proteins in Explicit Solvent Using Simulated Tempering}, journal = {J. Phys. Chem. B}, volume = {119}, number = {23}, year = {2015}, month = {jun}, pages = {6941{\textendash}6951}, author = {Zhang, Tong and Phuong Hoang Nguyen and Nasica-Labouze, Jessica and Mu, Yuguang and Philippe Derreumaux} } @article {2015|1646, title = {Molecular structure of the NQTrp inhibitor with the Alzheimer A beta 1-28 monomer}, journal = {Eur. J. Med. Chem.}, volume = {91}, year = {2015}, month = {feb}, pages = {43{\textendash}50}, doi = {10.1016/j.ejmech.2014.07.002}, author = {Tarus, Bogdan and Phuong Hoang Nguyen and Berthoumieu, Olivia and Faller, Peter and Doig, Andrew J. and Philippe Derreumaux} } @article {2015|1705, title = {Picosecond dissociation of amyloid fibrils with infrared laser: A nonequilibrium simulation study}, journal = {J. Chem. Phys.}, volume = {143}, number = {15}, year = {2015}, month = {oct}, pages = {155101}, doi = {10.1063/1.4933207}, author = {Man Hoang Viet and Philippe Derreumaux and Mai Suan Li and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2015|1745, title = {Picosecond melting of peptide nanotubes using an infrared laser: a nonequilibrium simulation study}, journal = {Phys. Chem. Chem. Phys.}, volume = {17}, number = {41}, year = {2015}, pages = {27275{\textendash}27280}, doi = {10.1039/c5cp04401d}, author = {Viet, Man Hoang and Phan Minh Truong and Philippe Derreumaux and Li, Mai Suan and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2015|1727, title = {Replica-exchange molecular dynamics simulation for understanding the initial process of amyloid peptide aggregation}, journal = {Mol. Simul.}, volume = {41}, number = {10-12}, year = {2015}, month = {aug}, pages = {1041{\textendash}1044}, author = {Nishikawa, Naohiro and Phuong Hoang Nguyen and Philippe Derreumaux and Okamoto, Yuko} } @article {2015|1714, title = {Structures of the Alzheimer{\textquoteright}s Wild-Type A beta 1-40 Dimer from Atomistic Simulations}, journal = {J. Phys. Chem. B}, volume = {119}, number = {33}, year = {2015}, pages = {10478{\textendash}10487}, doi = {10.1021/acs.jpcb.5b05593}, author = {Tarus, Bogdan and Thanh-Thuy Tran and Nasica-Labouze, Jessica and Fabio Sterpone and Phuong Hoang Nguyen and Philippe Derreumaux} } @conference {2015|1609, title = {What Computational Methods can Teach us about the Alzheimer-Protective Nature of A2V-and A2T-Mutant Amyloid-Beta Oligomers}, booktitle = {Biophys. J.}, volume = {108}, number = {2}, year = {2015}, pages = {204A-204A}, author = {Nasica-Labouze, Jessica and Tarus, Bogdan and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2014|1888, title = {Amyloid oligomer structure characterization from simulations: A general method}, journal = {J. Chem. Phys.}, volume = {140}, number = {9}, year = {2014}, month = {mar}, pages = {094105}, doi = {10.1063/1.4866902}, author = {Phuong Hoang Nguyen and Li, Mai Suan and Philippe Derreumaux} } @article {2014|1379, title = {Effect of the English Familial Disease Mutation (H6R) on the Monomers and Dimers of A beta 40 and A beta 42}, journal = {Acs Chem. Neurosci.}, volume = {5}, number = {8}, year = {2014}, month = {aug}, pages = {646{\textendash}657}, author = {Man Hoang Viet and Phuong Hoang Nguyen and Philippe Derreumaux and Li, Mai Suan} } @article {2014|1927, title = {Familial Alzheimer A2 V Mutation Reduces the Intrinsic Disorder and Completely Changes the Free Energy Landscape of the A beta 1-28 Monomer}, journal = {J. Phys. Chem. B}, volume = {118}, number = {2}, year = {2014}, month = {jan}, pages = {501{\textendash}510}, doi = {10.1021/jp4115404}, author = {Phuong Hoang Nguyen and Tarus, Bogdan and Philippe Derreumaux} } @article {2014|1798, title = {The OPEP protein model: from single molecules, amyloid formation, crowding and hydrodynamics to DNA/RNA systems}, journal = {Chem. Soc. Rev.}, volume = {43}, number = {13}, year = {2014}, pages = {4871{\textendash}4893}, doi = {10.1039/c4cs00048j}, author = {F. Sterpone and S. Melchionna and Pierre Tuffery and S. Pasquali and N. Mousseau and T. Cragnolini and Y Chebaro and J.-F. St-Pierre and M. Kalimeri and A. Barducci and Y. Laurin and A. Tek and Marc Baaden and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2013|1887, title = {Communication: Simulated tempering with fast on-the-fly weight determination}, journal = {J. Chem. Phys.}, volume = {138}, number = {6}, year = {2013}, month = {feb}, pages = {061102}, doi = {10.1063/1.4792046}, author = {Phuong Hoang Nguyen and Okamoto, Yuko and Philippe Derreumaux} } @article {2013|1924, title = {Conformational Ensemble and Polymorphism of the All-Atom Alzheimer{\textquoteright}s A beta(37-42) Amyloid Peptide Oligomers}, journal = {J. Phys. Chem. B}, volume = {117}, number = {19}, year = {2013}, month = {may}, pages = {5831{\textendash}5840}, doi = {10.1021/jp401563n}, author = {Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2013, title = {Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of A beta(40) and A beta(42)}, journal = {Acs Chem. Neurosci.}, volume = {4}, number = {11}, year = {2013}, month = {nov}, pages = {1446{\textendash}1457}, author = {Man Hoang Viet and Phuong Hoang Nguyen and Son Tung Ngo and Li, Mai Suan and Philippe Derreumaux} } @article {2013|1892, title = {Importance of the Ion-Pair Interactions in the OPEP Coarse-Grained Force Field: Parametrization and Validation}, journal = {J. Chem. Theory Comput.}, volume = {9}, number = {10}, year = {2013}, month = {oct}, pages = {4574{\textendash}4584}, doi = {10.1021/ct4003493}, author = {Sterpone, Fabio and Phuong Hoang Nguyen and Kalimeri, Maria and Philippe Derreumaux} } @article {2013|1806, title = {Replica-exchange molecular dynamics simulations of the amyloid-beta(16-22) fragments}, journal = {European Biophysics Journal with Biophysics Letters}, volume = {42}, number = {1}, year = {2013}, note = {9th European-Biophysical-Societies-Association Congress, Lisbon, PORTUGAL, JUL 13-17, 2013}, month = {jul}, pages = {S68}, author = {Nishikawa, N. and Phuong Hoang Nguyen and Philippe Derreumaux and Okamoto, Y.} } @article {2012|1955, title = {Configurational entropy: an improvement of the quasiharmonic approximation using configurational temperature}, journal = {Phys. Chem. Chem. Phys.}, volume = {14}, number = {20}, year = {2012}, pages = {877{\textendash}886}, doi = {10.1039/c1cp21779h}, author = {Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2012|1921, title = {Structures of A beta 17-42 Trimers in Isolation and with Five Small-Molecule Drugs Using a Hierarchical Computational Procedure}, journal = {J. Phys. Chem. B}, volume = {116}, number = {29, SI}, year = {2012}, month = {jul}, pages = {8412{\textendash}8422}, doi = {10.1021/jp2118778}, author = {Y Chebaro and Jiang, Ping and Zang, Tong and Mu, Yuguang and Phuong Hoang Nguyen and Mousseau, Normand and Philippe Derreumaux} } @article {2011|1473, title = {Coherent vibrational energy transfer along a peptide helix}, journal = {J. Chem. Phys.}, volume = {134}, number = {12}, year = {2011}, month = {mar}, author = {Kobus, Maja and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2011|1953, title = {Effects of all-atom force fields on amyloid oligomerization: replica exchange molecular dynamics simulations of the A beta(16-22) dimer and trimer}, journal = {Phys. Chem. Chem. Phys.}, volume = {13}, number = {20}, year = {2011}, pages = {9778{\textendash}9788}, doi = {10.1039/c1cp20323a}, author = {Phuong Hoang Nguyen and Li, Mai Suan and Philippe Derreumaux} } @inbook {2011|1573, title = {Exploring the energy landscape of small peptides and proteins by molecular dynamics simulations}, year = {2011}, publisher = {Wiley}, organization = {Wiley}, author = {G. Stock and A. Jain and L. Riccardi and Phuong Hoang Nguyen}, editor = {R. Schweitzer-Stenner} } @article {2011|1474, title = {Simulation of transient infrared spectra of a photoswitchable peptide}, journal = {J. Chem. Phys.}, volume = {135}, number = {12}, year = {2011}, month = {dec}, author = {Kobus, Maja and Lieder, Martin and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2010|1470, title = {Infrared signatures of the peptide dynamical transition: A molecular dynamics simulation study}, journal = {J. Chem. Phys.}, volume = {133}, number = {3}, year = {2010}, month = {jul}, author = {Kobus, Maja and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2010|1472, title = {Nonequilibrium molecular dynamics simulation of the energy transport through a peptide helix}, journal = {J. Chem. Phys.}, volume = {132}, number = {2}, year = {2010}, month = {jan}, author = {Phuong Hoang Nguyen and Park, Sang-Min and Stock, Gerhard} } @article {2010|1471, title = {Replica exchange simulation method using temperature and solvent viscosity}, journal = {J. Chem. Phys.}, volume = {132}, number = {14}, year = {2010}, month = {apr}, author = {Phuong Hoang Nguyen} } @article {2009|2018, title = {Energy Flow and Long-Range Correlations in Guanine-Binding Riboswitch: A Nonequilibrium Molecular Dynamics Study}, journal = {J. Phys. Chem. B}, volume = {113}, number = {27}, year = {2009}, month = {jul}, pages = {9340{\textendash}9347}, keywords = {Binding Sites, Computer Simulation, Energy Transfer, Guanine, Ligands, Models, Molecular, Nucleic Acid Conformation, RNA, Temperature}, doi = {10.1021/jp902013s}, author = {Phuong Hoang Nguyen and Philippe Derreumaux and Stock, Gerhard} } @article {2009|1398, title = {Estimating configurational entropy of complex molecules: A novel variable transformation approach}, journal = {Chem. Phys. Lett.}, volume = {468}, number = {1-3}, year = {2009}, month = {jan}, pages = {90{\textendash}93}, author = {Phuong Hoang Nguyen} } @article {2009|1486, title = {Free-Energy Landscape of RNA Hairpins Constructed via Dihedral Angle Principal Component Analysis}, journal = {J. Phys. Chem. B}, volume = {113}, number = {52}, year = {2009}, month = {dec}, pages = {16660{\textendash}16668}, author = {Riccardi, Laura and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2009|1469, title = {Molecular dynamics simulation of cooling: Heat transfer from a photoexcited peptide to the solvent}, journal = {J. Chem. Phys.}, volume = {131}, number = {18}, year = {2009}, month = {nov}, author = {Park, Sang-Min and Phuong Hoang Nguyen and Stock, Gerhard} } @inbook {2009|1568, title = {Nonequilibrium molecular dynamics simulation of photoinduced energy flow in peptides: theory meets experiment}, year = {2009}, publisher = {CRC Press}, organization = {CRC Press}, author = {Phuong Hoang Nguyen and P. Hamm and G. Stock}, editor = {D. Leitner and J. Straub} } @article {2008|1468, title = {Construction of the free energy landscape of biomolecules via dihedral angle principal component analysis}, journal = {J. Chem. Phys.}, volume = {128}, number = {24}, year = {2008}, month = {jun}, author = {Altis, Alexandros and Otten, Moritz and Phuong Hoang Nguyen and Hegger, Rainer and Stock, Gerhard} } @article {2008|1485, title = {Energy transport in peptide helices: A comparison between high- and low-energy excitations}, journal = {J. Phys. Chem. B}, volume = {112}, number = {30}, year = {2008}, month = {jul}, pages = {9091{\textendash}9099}, author = {Backus, Ellen H. G. and Phuong Hoang Nguyen and Botan, Virgiliu and Pfister, Rolf and Moretto, Alessandro and Crisma, Marco and Toniolo, Claudio and Stock, Gerhard and Hamm, Peter} } @article {2008|1397, title = {Nonadiabatic vibrational dynamics and spectroscopy of peptides: A quantum-classical description}, journal = {Chem. Phys.}, volume = {347}, number = {1-3}, year = {2008}, month = {may}, pages = {208{\textendash}217}, author = {Kobus, Maja and Gorbunov, Roman D. and Phuong Hoang Nguyen and Stock, Gerhard} } @conference {2008|1545, title = {OPERA: An OPtimized coarsed-grained Energy model for RnA}, booktitle = {Publication Series of the John von Neumann Institute for Computing NIC Series}, volume = {40}, year = {2008}, pages = {185{\textendash}187}, author = {C. Colas and Phuong Hoang Nguyen and J-C. Gelly and Philippe Derreumaux} } @article {2008|1484, title = {Structural Flexibility of a Helical Peptide Regulates Vibrational Energy Transport Properties}, journal = {J. Phys. Chem. B}, volume = {112}, number = {48}, year = {2008}, month = {dec}, pages = {15487{\textendash}15492}, author = {Backus, Ellen H. G. and Phuong Hoang Nguyen and Botan, Virgiliu and Moretto, Alessandro and Crisma, Marco and Toniolo, Claudio and Zerbe, Oliver and Stock, Gerhard and Hamm, Peter} } @article {2007|1542, title = {Conformational states and folding pathways of peptides revealed by principal-independent component analyses}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {67}, number = {3}, year = {2007}, month = {may}, pages = {579{\textendash}592}, author = {Phuong Hoang Nguyen} } @article {2007, title = {Dihedral angle principal component analysis of molecular dynamics simulations}, journal = {J. Chem. Phys.}, volume = {126}, number = {24}, year = {2007}, month = {jun}, author = {Altis, Alexandros and Phuong Hoang Nguyen and Hegger, Rainer and Stock, Gerhard} } @article {2007|1534, title = {Energy transport in peptide helices}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {104}, number = {31}, year = {2007}, month = {jul}, pages = {12749{\textendash}12754}, author = {Botan, Virgiliu and Backus, Ellen H. G. and Pfister, Rolf and Moretto, Alessandro and Crisma, Marco and Toniolo, Claudio and Phuong Hoang Nguyen and Stock, Gerhard and Hamm, Peter} } @article {2007|1522, title = {How complex is the dynamics of peptide folding?}, journal = {Phys. Rev. Lett.}, volume = {98}, number = {2}, year = {2007}, month = {jan}, author = {Hegger, Rainer and Altis, Alexandros and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2007|1535, title = {Monomer adds to preformed structured oligomers of A beta-peptides by a two-stage dock-lock mechanism}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {104}, number = {1}, year = {2007}, month = {jan}, pages = {111{\textendash}116}, author = {Phuong Hoang Nguyen and Li, Mai Suan and Stock, Gerhard and Straub, John E. and Thirumalai, D.} } @article {2007|1467, title = {Quantum-classical description of the amide I vibrational spectrum of trialanine}, journal = {J. Chem. Phys.}, volume = {126}, number = {5}, year = {2007}, month = {feb}, author = {Gorbunov, Roman D. and Phuong Hoang Nguyen and Kobus, Maja and Stock, Gerhard} } @article {2007|1489, title = {Structure and dynamics of the homologous series of alanine peptides: A joint molecular dynamics/NMR study}, journal = {J. Am. Chem. Soc.}, volume = {129}, number = {5}, year = {2007}, month = {feb}, pages = {1179{\textendash}1189}, author = {Graf, Juergen and Phuong Hoang Nguyen and Stock, Gerhard and Schwalbe, Harald} } @article {2006|1541, title = {Complexity of free energy landscapes of peptides revealed by nonlinear principal component analysis}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {65}, number = {4}, year = {2006}, month = {dec}, pages = {898{\textendash}913}, author = {Phuong Hoang Nguyen} } @article {2006|1466, title = {Improved Wang-Landau sampling through the use of smoothed potential-energy surfaces}, journal = {J. Chem. Phys.}, volume = {124}, number = {15}, year = {2006}, month = {apr}, author = {Phuong Hoang Nguyen and Mittag, E and Torda, AE and Stock, G} } @article {2006|1396, title = {Nonequilibrium molecular dynamics simulation of a photoswitchable peptide}, journal = {Chem. Phys.}, volume = {323}, number = {1}, year = {2006}, month = {mar}, pages = {36{\textendash}44}, author = {Phuong Hoang Nguyen and Stock, G} } @article {2006|1389, title = {Photoinduced conformational dynamics of a photoswitchable peptide: A nonequilibrium molecular dynamics simulation study}, journal = {Biophys. J.}, volume = {91}, number = {4}, year = {2006}, month = {aug}, pages = {1224{\textendash}1234}, author = {Phuong Hoang Nguyen and Gorbunov, Roman D. and Stock, Gerhard} } @article {2005|1540, title = {Energy landscape of a small peptide revealed by dihedral angle principal component analysis}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {58}, number = {1}, year = {2005}, month = {jan}, pages = {45{\textendash}52}, author = {Mu, YG and Phuong Hoang Nguyen and Stock, G} } @article {2005|1538, title = {Free energy landscape and folding mechanism of a beta-hairpin in explicit water: A replica exchange molecular dynamics study}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {61}, number = {4}, year = {2005}, month = {dec}, pages = {795{\textendash}808}, author = {Phuong Hoang Nguyen and Stock, G and Mittag, E and Hu, CK and Li, MS} } @article {2005|1539, title = {Structure and energy landscape of a photoswitchable peptide: A replica exchange molecular dynamics study}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {60}, number = {3}, year = {2005}, month = {aug}, pages = {485{\textendash}494}, author = {Phuong Hoang Nguyen and Mu, YG and Stock, G} } @article {2003|1464, title = {Nonequilibrium molecular-dynamics study of the vibrational energy relaxation of peptides in water}, journal = {J. Chem. Phys.}, volume = {119}, number = {21}, year = {2003}, month = {dec}, pages = {11350{\textendash}11358}, author = {Phuong Hoang Nguyen and Stock, G} }