@misc{pan_zhang_xu_man_roland_weninger_sagui_2021, title={Molecular conformations and dynamics of nucleotide repeats associated with neurodegenerative diseases: double helices and CAG hairpin loops}, volume={19}, ISSN={["2001-0370"]}, DOI={10.1016/j.csbj.2021.04.037}, abstractNote={Pathogenic DNA secondary structures have been identified as a common and causative factor for expansion in trinucleotide, hexanucleotide, and other simple sequence repeats. These expansions underlie about fifty neurological and neuromuscular disorders known as “anticipation diseases”. Cell toxicity and death have been linked to the pathogenic conformations and functional changes of the RNA transcripts, of DNA itself and, when trinucleotides are present in exons, of the translated proteins. We review some of our results for the conformations and dynamics of pathogenic structures for both RNA and DNA, which include mismatched homoduplexes formed by trinucleotide repeats CAG and GAC; CCG and CGG; CTG(CUG) and GTC(GUC); the dynamics of DNA CAG hairpins; mismatched homoduplexes formed by hexanucleotide repeats (GGGGCC) and (GGCCCC); and G-quadruplexes formed by (GGGGCC) and (GGGCCT). We also discuss the dynamics of strand slippage in DNA hairpins formed by CAG repeats as observed with single-molecule Fluorescence Resonance Energy Transfer. This review focuses on the rich behavior exhibited by the mismatches associated with these simple sequence repeat noncanonical structures.}, journal={COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL}, author={Pan, Feng and Zhang, Yuan and Xu, Pengning and Man, Viet Hoang and Roland, Christopher and Weninger, Keith and Sagui, Celeste}, year={2021}, pages={2819–2832} }
 @article{pan_man_roland_sagui_2017, title={Structure and Dynamics of DNA and RNA Double Helices of CAG and GAC Trinucleotide Repeats}, volume={113}, ISSN={["1542-0086"]}, DOI={10.1016/j.bpj.2017.05.041}, abstractNote={CAG trinucleotide repeats are known to cause 10 late-onset progressive neurodegenerative disorders as the repeats expand beyond a threshold, whereas GAC repeats are associated with skeletal dysplasias and expand from the normal five to a maximum of seven repeats. The TR secondary structure is believed to play a role in CAG expansions. We have carried out free energy and molecular dynamics studies to determine the preferred conformations of the A-A noncanonical pairs in (CAG)n and (GAC)n trinucleotide repeats (n = 1, 4) and the consequent changes in the overall structure of the RNA and DNA duplexes. We find that the global free energy minimum corresponds to A-A pairs stacked inside the core of the helix with anti-anti conformations in RNA and (high-anti)-(high-anti) conformations in DNA. The next minimum corresponds to anti-syn conformations, whereas syn-syn conformations are higher in energy. Transition rates of the A-A conformations are higher for RNA than DNA. Mechanisms for these various transitions are identified. Additional structural and dynamical aspects of the helical conformations are explored, with a focus on contrasting CAG and GAC duplexes. The neutralizing ion distribution around the noncanonical pairs is described.}, number={1}, journal={BIOPHYSICAL JOURNAL}, author={Pan, Feng and Man, Viet Hoang and Roland, Christopher and Sagui, Celeste}, year={2017}, month={Jul}, pages={19–36} }
 @article{man_pan_sagui_roland_2016, title={Comparative melting and healing of B-DNA and Z-DNA by an infrared laser pulse}, volume={144}, ISSN={["1089-7690"]}, DOI={10.1063/1.4945340}, abstractNote={We explore the use of a fast laser melting simulation approach combined with atomistic molecular dynamics simulations in order to determine the melting and healing responses of B-DNA and Z-DNA dodecamers with the same d(5′-CGCGCGCGCGCG-3′)2 sequence. The frequency of the laser pulse is specifically tuned to disrupt Watson-Crick hydrogen bonds, thus inducing melting of the DNA duplexes. Subsequently, the structures relax and partially refold, depending on the field strength. In addition to the inherent interest of the nonequilibrium melting process, we propose that fast melting by an infrared laser pulse could be used as a technique for a fast comparison of relative stabilities of same-sequence oligonucleotides with different secondary structures with full atomistic detail of the structures and solvent. This could be particularly useful for nonstandard secondary structures involving non-canonical base pairs, mismatches, etc.}, number={14}, journal={JOURNAL OF CHEMICAL PHYSICS}, author={Man, Viet Hoang and Pan, Feng and Sagui, Celeste and Roland, Christopher}, year={2016}, month={Apr} }
 @article{viet_derreumaux_nguyen_2016, title={Nonequilibrium all-atom molecular dynamics simulation of the bubble cavitation and application to dissociate amyloid fibrils}, volume={145}, ISSN={["1089-7690"]}, DOI={10.1063/1.4966263}, abstractNote={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 Aβ 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.}, number={17}, journal={JOURNAL OF CHEMICAL PHYSICS}, author={Viet, Man Hoang and Derreumaux, Philippe and Nguyen, Phuong H.}, year={2016}, month={Nov} }
 @article{man_van-oanh_derreumaux_li_roland_sagui_nguyen_2016, title={Picosecond infrared laser-induced all-atom nonequilibrium molecular dynamics simulation of dissociation of viruses}, volume={18}, ISSN={["1463-9084"]}, DOI={10.1039/c5cp07711g}, abstractNote={Laser-induced all-atom nonequilibrium molecular dynamics simulation of virus dissociation.}, number={17}, journal={PHYSICAL CHEMISTRY CHEMICAL PHYSICS}, author={Man, Viet Hoang and Van-Oanh, Nguyen-Thi and Derreumaux, Philippe and Li, Mai Suan and Roland, Christopher and Sagui, Celeste and Nguyen, Phuong H.}, year={2016}, month={May}, pages={11951–11958} }
 @article{viet_derreumaux_nguyen_2015, title={Communication: Multiple atomistic force fields in a single enhanced sampling simulation}, volume={143}, ISSN={["1089-7690"]}, DOI={10.1063/1.4926535}, abstractNote={The main concerns of biomolecular dynamics simulations are the convergence of the conformational sampling and the dependence of the results on the force fields. While the first issue can be addressed by employing enhanced sampling techniques such as simulated tempering or replica exchange molecular dynamics, repeating these simulations with different force fields is very time consuming. Here, we propose an automatic method that includes different force fields into a single advanced sampling simulation. Conformational sampling using three all-atom force fields is enhanced by simulated tempering and by formulating the weight parameters of the simulated tempering method in terms of the energy fluctuations, the system is able to perform random walk in both temperature and force field spaces. The method is first demonstrated on a 1D system and then validated by the folding of the 10-residue chignolin peptide in explicit water.}, number={2}, journal={JOURNAL OF CHEMICAL PHYSICS}, author={Viet, Man Hoang and Derreumaux, Philippe and Nguyen, Phuong H.}, year={2015}, month={Jul} }
 @article{man_roland_sagui_2015, title={Structural Determinants of Polyglutamine Protofibrils and Crystallites}, volume={6}, ISSN={["1948-7193"]}, DOI={10.1021/cn500358g}, abstractNote={Nine inherited neurodegenerative diseases are associated with the expansion of the CAG codon. Once the translated polyglutamine expansion becomes longer than ~36 residues, it triggers the formation of intraneural protein aggregates that often display the signature of cross-β amyloid fibrils. Here, we use fully atomistic molecular dynamics simulations to probe the structural stability and conformational dynamics of both previously proposed and new polyglutamine aggregate models. We test the relative stability of parallel and antiparallel β sheets, and characterize possible steric interfaces between neighboring sheets and the effects of different alignments of the side-chain carboxamide dipoles. Results indicate that (i) different initial oligomer structures converge to crystals consistent with available diffraction data, after undergoing cooperative side-chain rotational transitions and quarter-stagger displacements on a microsecond time scale, (ii) structures previously deemed stable on a hundred nanosecond time scale are unstable over the microsecond time scale, and (iii) conversely, structures previously deemed unstable did not account for the correct side-chain packing and once the correct symmetry is considered the structures become stable for over a microsecond, due to tightly interdigitated side chains, which lock into highly regular polar zippers with inter-side-chain and backbone-side-chain hydrogen bonds. With these insights, we built Q40 monomeric models with different combinations of arc and hairpin turns and tested them for stability. The stable monomers were further probed as a function of repeat length. Our results are consistent with the aggregation threshold. These results explain and reconcile previously reported experimental and model discrepancies about polyglutamine aggregate structures.}, number={4}, journal={ACS CHEMICAL NEUROSCIENCE}, author={Man, Viet Hoang and Roland, Christopher and Sagui, Celeste}, year={2015}, month={Apr}, pages={632–645} }