Unequal Intra-layer Coupling in a Bilayer Driven Lattice Gas

The system under study is a twin-layered square lattice gas at half-filling, being driven to non-equilibrium steady states by a large, finite `electric' field. By making intra-layer couplings unequal we were able to extend the phase diagram obtained by Hill, Zia and Schmittmann (1996) and found that the tri-critical point, which separates the phase regions of the stripped (S) phase (stable at positive interlayer interactions J_3), the filled-empty (FE) phase (stable at negative J_3) and disorder (D), is shifted even further into the negative J_3 region as the coupling traverse to the driving field increases. Many transient phases to the S phase at the S-FE boundary were found to be long-lived. We also attempted to test whether the universality class of D-FE transitions under a drive is still Ising. Simulation results suggest a value of 1.75 for the exponent gamma but a value close to 2.0 for the ratio gamma/nu. We speculate that the D-FE second order transition is different from Ising near criticality, where observed first-order-like transitions between FE and its "local minimum" cousin occur during each simulation run.Comment: 29 pages, 19 figure

Bacterial flagellar filament protein unfolding/refolding mechanisms studied by molecular dynamics simulations

報告番号: 甲24184 ; 学位授与年月日: 2008-09-30 ; 学位の種別: 課程博士 ; 学位の種類: 博士(科学) ; 学位記番号: 博創域第401号 ; 研究科・専攻: 新領域創成科学研究科情報生命科学専

分子動力学シミュレーションによる細菌べん毛繊維蛋白質のアンフォールディング

University of Tokyo (東京大学

Coarse-Grained Models Reveal Functional Dynamics – II. Molecular Dynamics Simulation at the Coarse-Grained Level – Theories and Biological Applications

Molecular dynamics (MD) simulation has remained the most indispensable tool in studying equilibrium/non-equilibrium conformational dynamics since its advent 30 years ago. With advances in spectroscopy accompanying solved biocomplexes in growing sizes, sampling their dynamics that occur at biologically interesting spatial/temporal scales becomes computationally intractable; this motivated the use of coarse-grained (CG) approaches. CG-MD models are used to study folding and conformational transitions in reduced resolution and can employ enlarged time steps due to the a bsence of some of the fastest motions in the system. The Boltzmann-Inversion technique, heavily used in parameterizing these models, provides a smoothed-out effective potential on which molecular conformation evolves at a faster pace thus stretching simulations into tens of microseconds. As a result, a complete catalytic cycle of HIV-1 protease or the assembly of lipid-protein mixtures could be investigated by CG-MD to gain biological insights. In this review, we survey the theories developed in recent years, which are categorized into Folding-based and Molecular-Mechanics-based. In addition, physical bases in the selection of CG beads/time-step, the choice of effective potentials, representation of solvent, and restoration of molecular representations back to their atomic details are systematically discussed

Coarse-Grained Models Reveal Functional Dynamics - I. Elastic Network Models – Theories, Comparisons and Perspectives

Abstract: In this review, we summarize the progress on coarse-grained elastic network models (CG-ENMs) in the past decade. Theories were formulated to allow study of conformational dynamics in time/space frames of biological interest. Several highlighted models and their underlined hypotheses are introduced in physical depth. Important ENM offshoots, motivated to reproduce experimental data as well as to address the slow-mode-encoded configurational transitions, are also introduced. With the theoretical developments, computational cost is significantly reduced due to simplified potentials and coarse-grained schemes. Accumulating wealth of data suggest that ENMs agree equally well with experiment in describing equilibrium dynamics despite their distinct potentials and levels of coarse-graining. They however do differ in the slowest motional components that are essential to address large conformational changes of functional significance. The difference stems from the dissimilar curvatures of the harmonic energy wells described for each model. We also provide our views on the predictability of ‘open to close’ (open→close) transitions of biomolecules on the basis of conformational selection theory. Lastly, we address the limitations of the ENM formalism which are partially alleviated by the complementary CGMD approach, to be introduced in the second paper of this two-part series

Site-specific peroxidation modulates lipid bilayer mechanics

Peroxidation of plasma membranes, characterized by oxidative attack of lipidic carbon–carbon double bonds in unsaturated fatty acids, has been identified as an important biochemical event in multiple pathological conditions, including neurodegenerative diseases, atherosclerosis, diabetes, preeclampsia, aging, cancer, etc. Changes to the lipid bilayer structure as a result of lipid peroxidation may lead to lipid membrane malfunction, and consequently initiate further downstream biochemical cascades. However, how lipid peroxidation modulates the mechanical properties of lipid membranes remains largely controversial. In this study, we investigate the peroxidation of lipids with polyunsaturated fatty acid tails using molecular dynamics simulations. By systematically varying the oxidation site, we find that lipid peroxidation alters the biophysical properties of bilayer membrane in a peroxidation site-specific manner. Specifically, our results suggest that peroxidation at sites in the bilayer interior disturbs and softens the membrane, whereas peroxidation at sites near the membrane–water interface results in a more ordered and stiffer membrane. Such a peroxidation site-specific modulation of lipid membrane mechanics provides an explanation for the contradictory results obtained in previous experiments. Our study paves the way for an improved understanding of the initiation of the downstream cellular dysfunction caused by lipid peroxidation.Ministry of Education (MOE)Nanyang Technological UniversityAccepted versionY.S., K.J.H. and C.H. acknowledge the financial support by the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD086325). K.J.H. would like to acknowledge financial support from Nanyang Technological University (start-up grant M4082428.050). C.H. would also like to acknowledge financial support from Nanyang Technological University (start-up grant M4082352.050) and the Ministry of Education, Singapore, under its Academic Research Fund Tier 1 (M4012229.050). The computational work for this article was fully performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg)

Chloroplast membrane lipid remodeling protects against dehydration by limiting membrane fusion and distortion

Dehydration damages the structural integrity of the chloroplast membrane and, consequently, the normal photosynthetic function of this organelle. Remodeling of galactolipids by converting monogalactosyl-diacylglycerol (MGDG) to digalactosyl-diacylglycerol (DGDG) and oligo-galactolipids is an effective adaptation strategy for protecting against dehydration damage to the chloroplast membrane. However, detailed molecular mechanisms are missing. In this study, by performing molecular-level simulations of bi-lamellar membranes under various dehydration conditions, we find that MGDG-to-DGDG remodeling protects the chloroplast membrane in a unique manner by simultaneously dictating both the extent and the pattern of fusion stalks formed with the apposed membrane. Specifically, MGDG-rich membranes form elongated stalks at a moderate dehydration level, whereas DGDG-rich membranes form smaller, rounded stalks. Simulations of wild-type and mutant Arabidopsis (Arabidopsis thaliana) outer chloroplast membranes further confirm that the mutant membrane without galactolipid remodeling is more susceptible to membrane fusion due to its higher MGDG content. Our work reveals the underlying physical mechanisms that govern the pattern and extent of membrane fusion structures, paving the way for rational genetic engineering of crops with improved dehydration tolerance.Ministry of Education (MOE)Nanyang Technological UniversityAccepted versionThis work was supported by Nanyang Technological University under its Accelerating Creativity and Excellence (ACE) grant (grant no. NTU–ACE2020-07 to W.M., K.J.H and C.H.), Nanyang Technological University start-up grants (grant nos. M4082428 to K.J.H. and M4082352 to C.H.), and Ministry of Education, Singapore, under its Academic Research Fund Tier 1 (grant no. RG92/19)