xinmeng

• Ahmad, Ahmad Ali; Mors, Mira; Carrer, Manuel; Li, Xinmeng; Bilokapić, Silvija & Halić, Mario [Show all 8 contributors for this article] (2025). Structure and dynamics of 2x(CENP-A/H4)2 octasome reveal a possible intermediate in centromeric chromatin. Life Science Alliance (LSA). 9(3). doi: 10.26508/lsa.202503377. Full text in Research Archive Show summary

  The centromere is a part of the chromosome that is essential for the even segregation of duplicated chromosomes during cell division. It is epigenetically defined by the presence of the histone H3 variant CENP-A. CENP-A associates specifically with a group of 16 proteins that form the constitutive centromere-associated network (CCAN) of proteins. In mitosis, the kinetochore forms on the CCAN to connect the duplicated chromosomes to the microtubules protruding from the cell poles. Previous studies have shown that CENP-A replaces H3 in nucleosomes, and recently, the structures of CENP-A-containing nucleosomes in complex with CCANs have been revealed, but they show only a limited interaction between CCANs and CENP-A. Here, we report the cryo-EM structure of 2x(CENP-A/H4)2 octasomes assembled on DNA in the absence of H2A/H2B histone dimer and speculate how (CENP-A/H4)2 tetrasomes might serve as a platform for CCAN organization.

• Dsouza, Lolita; Gupta, Karthick Babu Sai Sankar; Li, Xinmeng; Erić, Vesna; Luo, Yusen & Huijser, Annemarie [Show all 13 contributors for this article] (2025). Conformational Dynamics of Bacteriochlorophyll c in Chlorosomes from the bchQ Mutant of Chlorobaculum tepidum. Journal of Physical Chemistry B. ISSN 1520-6106. 129(8), p. 2129–2137. doi: 10.1021/acs.jpcb.4c04731. Full text in Research Archive Show summary

  In contrast to the common viewpoint that bacteriochlorophyll (BChl) motion is largely absent within the chlorosome assembly, physics-based modeling points to a crucial role of the nanoscale librational motion of the macrocycle for the transfer of excitons. To elucidate this motion experimentally, compositional uniformity and high sensitivity are required. We focused on uniformly 13C labeled chlorosome preparations from the bchQ mutant Chlorobaculum tepidum with significantly enhanced structural homogeneity. The librational motion is characterized using Rotational Echo DOuble Resonance (REDOR), and in addition, the impact of temperature on specific functionalities within BChl molecules is studied with 1-dimensional and 2-dimensional dipolar and scalar-based MAS NMR measurements. Results show the gradual freezing of the tails and side chains of the BChls with decreasing temperature. However, the librational motion analyzed by measuring the 5C–H dipolar coupling strength obtained from REDOR data sets persists at different temperatures. REDOR simulations show a close match to the experimental dephasing frequency of oscillation for a dipolar coupling strength of 17.5 ± 0.5 kHz which is considerably less than the dipolar coupling strength of 22.7 kHz in the rigid limit. Following a two-site jump model, we arrive at an estimate for BChl libration sampling at an angle of θ = 48 ± 4°, corroborating that the macrocycle indeed experiences significant librational motion on a time scale that is short compared to the NMR measurement time. This finding is in full quantitative support of the dominant rotational motion exhibited by the BChl macrocycle estimated from early MD simulations.

• Sen, Samiran; Cezar, Henrique Musseli; Ledum, Morten; Li, Xinmeng & Cascella, Michele (2024). Phase Coexistence in Hamiltonian Hybrid Particle-Field Theory Using a Multi-Gaussian Approach. Journal of Physical Chemistry B. ISSN 1520-6106. 128(47), p. 11739–11747. doi: 10.1021/acs.jpcb.4c05525. Full text in Research Archive Show summary

  This study introduces an implementation of multiple Gaussian filters within the Hamiltonian hybrid particle-field (HhPF) theory, aimed at capturing phase co-existence phenomena in mesoscopic molecular simulations. By employing a linear combination of two Gaussians, we demonstrate that HhPF can generate potentials with attractive and steric components analogous to Lennard-Jones potentials, which are crucial for modeling phase co-existence. We compare the performance of this method with the Multi-Gaussian Core Model (MGCM) in simulating liquid-gas coexistence for a single-component system across various densities and temperatures. Our results show that HhPF effectively captures detailed information on phase co-existence and interfacial phenomena, including micro-configuration transitions and increased interfacial fluctuations at higher temperatures. Notably, the phase boundaries obtained from HhPF simulations align more closely with those of Lennard-Jones systems compared to the MGCM results. This work advances the hybrid particle-field methodology to address phase co-existence without requiring modifications to the equation of state or introducing additional interaction energy functional terms, offering a promising approach for mesoscale molecular simulations of complex systems.

• Sen, Samiran; Cezar, Henrique Musseli; Ledum, Morten; Li, Xinmeng & Cascella, Michele (2024). Phase coexistence in Hamiltonian hybrid particle--field theory using a Multi-Gaussian approach. ChemRxiv. ISSN 2573-2293. doi: 10.26434/chemrxiv-2024-cm4xr-v2. Full text in Research Archive
• Dsouza, Lolita; Li, Xinmeng; Erić, Vesna; Huijser, Annemarie; Jansen, Thomas L. C. & Holzwarth, Alfred R. [Show all 12 contributors for this article] (2024). An integrated approach towards extracting structural characteristics of chlorosomes from a bchQ mutant of Chlorobaculum tepidum. Physical Chemistry, Chemical Physics - PCCP. ISSN 1463-9076. doi: 10.1039/d4cp00221k. Full text in Research Archive Show summary

  Chlorosomes, the photosynthetic antenna complexes of green sulfur bacteria, are paradigms for light-harvesting elements in artificial designs, owing to their efficient energy transfer without protein participation. We combined magic angle spinning (MAS) NMR, optical spectroscopy and cryogenic electron microscopy (cryo-EM) to characterize the structure of chlorosomes from a bchQ mutant of Chlorobaculum tepidum. The chlorosomes of this mutant have a more uniform composition of bacteriochlorophyll (BChl) with a predominant homolog, [8Ethyl, 12Ethyl] BChl c, compared to the wild type (WT). Nearly complete 13C chemical shift assignments were obtained from well-resolved homonuclear 13C–13C RFDR data. For proton assignments heteronuclear 13C–1H (hCH) data sets were collected at 1.2 GHz spinning at 60 kHz. The CHHC experiments revealed intermolecular correlations between 132/31, 132/32, and 121/31, with distance constraints of less than 5 Å. These constraints indicate the syn–anti parallel stacking motif for the aggregates. Fourier transform cryo-EM data reveal an axial repeat of 1.49 nm for the helical tubular aggregates, perpendicular to the inter-tube separation of 2.1 nm. This axial repeat is different from WT and is in line with BChl syn–anti stacks running essentially parallel to the tube axis. Such a packing mode is in agreement with the signature of the Qy band in circular dichroism (CD). Combining the experimental data with computational insight suggests that the packing for the light-harvesting function is similar between WT and bchQ, while the chirality within the chlorosomes is modestly but detectably affected by the reduced compositional heterogeneity in bchQ.

• Erić, Vesna; Li, Xinmeng; Dsouza, Lolita; Huijser, Annemarie; Holzwarth, Alfred R. & Buda, Francesco [Show all 9 contributors for this article] (2024). Observation of Dark States in Two-Dimensional Electronic Spectra of Chlorosomes. Journal of Physical Chemistry B. ISSN 1520-6106. 128(15), p. 3575–3584. doi: 10.1021/acs.jpcb.4c00067. Full text in Research Archive Show summary

  Observations of low-lying dark states in several photosynthetic complexes challenge our understanding of the mechanisms behind their efficient energy transfer processes. Computational models are necessary for providing novel insights into the nature and function of dark states, especially since these are not directly accessible in spectroscopy experiments. Here, we will focus on signatures of dark-type states in chlorosomes, a light-harvesting complex from green sulfur bacteria well-known for uniting a broad absorption band with very efficient energy transfer. In agreement with experiments, our simulations of two-dimensional electronic spectra capture the ultrafast exciton transfer occurring in 100s of femtoseconds within a single chlorosome cylinder. The sub-100 fs process corresponds to relaxation within the single-excitation manifold in a single chlorosome tube, where all initially created populations in the bright exciton states are quickly transferred to dark-type exciton states. Structural inhomogeneities on the local scale cause a redistribution of the oscillator strength, leading to the emergence of these dark-type exciton states, which dominate ultrafast energy transfer. The presence of the dark-type exciton states suppresses energy loss from an isolated chlorosome via fluorescence quenching, as observed experimentally. Our results further question whether relaxation to dark-exciton states is a leading process or merely competes with transfer to the baseplate within the photosynthetic apparatus of green sulfur bacteria.

• Ledum, Morten; Sen, Samiran; Li, Xinmeng; Carrer, Manuel; Feng, Yu & Cascella, Michele [Show all 7 contributors for this article] (2023). HylleraasMD: A Domain Decomposition-Based Hybrid Particle-Field Software for Multiscale Simulations of Soft Matter. Journal of Chemical Theory and Computation. ISSN 1549-9618. doi: 10.1021/acs.jctc.3c00134. Full text in Research Archive Show summary

  We present HylleraasMD (HyMD), a comprehensive implementation of the recently proposed Hamiltonian formulation of hybrid particle-field molecular dynamics. The methodology is based on a tunable, grid-independent length-scale of coarse graining, obtained by filtering particle densities in reciprocal space. This enables systematic convergence of energies and forces by grid refinement, also eliminating nonphysical force aliasing. Separating the time integration of fast modes associated with internal molecular motion from slow modes associated with their density fields, we enable the first time-reversible, energy-conserving hybrid particle-field simulations. HyMD comprises the optional use of explicit electrostatics, which, in this formalism, corresponds to the long-range potential in particle-mesh Ewald. We demonstrate the ability of HyMD to perform simulations in the microcanonical and canonical ensembles with a series of test cases, comprising lipid bilayers and vesicles, surfactant micelles, and polypeptide chains, comparing our results to established literature. An on-the-fly increase of the characteristic coarse-grain length significantly speeds up dynamics, accelerating self-diffusion and leading to expedited aggregation. Exploiting this acceleration, we find that the time scales involved in the self-assembly of polymeric structures can lie in the tens to hundreds of picoseconds instead of the multimicrosecond regime observed with comparable coarse-grained models.

• Bjørnestad, Victoria Ariel; Li, Xinmeng; Tribet, Christophe; Lund, Reidar & Cascella, Michele (2023). Micelle kinetics of photoswitchable surfactants: Self-assembly pathways and relaxation mechanisms. Journal of Colloid and Interface Science. ISSN 0021-9797. 646, p. 883–899. doi: 10.1016/j.jcis.2023.05.057. Full text in Research Archive Show summary

  Hypothesis: A key question in the kinetics of surfactant self-assembly is whether exchange of unimers or fusion/fission of entire micelles is the dominant pathway. In this study, an isomerizable surfactant is used to explore fundamental out-of-equilibrium kinetics and mechanisms for growth and dissolution of micelles. Experiments: The kinetics of cationic surfactant 4-butyl-4'-(3-trimethylammoniumpropoxy)-phenylazobenzene was studied using molecular dynamics simulations. The fusion and exchange processes were investigated using umbrella sampling. Equilibrium states were validated by comparison with small-angle X-ray scattering data. The photo-isomerization event was simulated by modifying the torsion potential of the photo-responsive group to emulate the trans-to-cis transition. Findings: Micelle growth is dominated by unimer exchange processes, whereas, depending on the conditions, dissolution can occur both through fission and unimer expulsion. Fusion barriers increase steeply with the aggregation number making this an unlikely pathway to equilibrium for micelles of sizes that fit with the experimental data. The barriers for unimer expulsion remain constant and are much lower for unimer insertion, making exchange more likely at high aggregation. When simulating photo-conversion events, both fission and a large degree of unimer expulsion can occur depending on the extent of the out-of-equilibrium stress that is put on the system.

• Frehan, Sean K.; Dsouza, Lolita; Li, Xinmeng; Eríc, Vesna; Jansen, Thomas L. C. & Mul, Guido [Show all 11 contributors for this article] (2023). Photon Energy-Dependent Ultrafast Exciton Transfer in Chlorosomes of Chlorobium tepidum and the Role of Supramolecular Dynamics. Journal of Physical Chemistry B. ISSN 1520-6106. 127(35), p. 7581–7589. doi: 10.1021/acs.jpcb.3c05282. Full text in Research Archive Show summary

  The antenna complex of green sulfur bacteria, the chlorosome, is one of the most efficient supramolecular systems for efficient long-range exciton transfer in nature. Femtosecond transient absorption experiments provide new insight into how vibrationally induced quantum overlap between exciton states supports highly efficient long-range exciton transfer in the chlorosome of Chlorobium tepidum. Our work shows that excitation energy is delocalized over the chlorosome in <1 ps at room temperature. The following exciton transfer to the baseplate occurs in ∼3 to 5 ps, in line with earlier work also performed at room temperature, but significantly faster than at the cryogenic temperatures used in previous studies. This difference can be attributed to the increased vibrational motion at room temperature. We observe a so far unknown impact of the excitation photon energy on the efficiency of this process. This dependency can be assigned to distinct optical domains due to structural disorder, combined with an exciton trapping channel competing with exciton transfer toward the baseplate. An oscillatory transient signal damped in <1 ps has the highest intensity in the case of the most efficient exciton transfer to the baseplate. These results agree well with an earlier computational finding of exciton transfer driven by low-frequency rotational motion of molecules in the chlorosome. Such an exciton transfer process belongs to the quantum coherent regime, for which the Förster theory for intermolecular exciton transfer does not apply. Our work hence strongly indicates that structural flexibility is important for efficient long-range exciton transfer in chlorosomes.

• Erić, Vesna; Castro, Jorge Luis; Li, Xinmeng; Dsouza, Lolita; Frehan, Sean K. & Huijser, Annemarie [Show all 11 contributors for this article] (2023). Ultrafast Anisotropy Decay Reveals Structure and Energy Transfer in Supramolecular Aggregates. Journal of Physical Chemistry B. ISSN 1520-6106. 127(34), p. 7487–7496. doi: 10.1021/acs.jpcb.3c04719. Full text in Research Archive Show summary

  Chlorosomes from green bacteria perform the most efficient light capture and energy transfer, as observed among natural light-harvesting antennae. Hence, their unique functional properties inspire developments in artificial light-harvesting and molecular optoelectronics. We examine two distinct organizations of the molecular building blocks as proposed in the literature, demonstrating how these organizations alter light capture and energy transfer, which can serve as a mechanism that the bacteria utilize to adapt to changes in light conditions. Spectral simulations of polarization-resolved two-dimensional electronic spectra unravel how changes in the helicity of chlorosomal aggregates alter energy transfer. We show that ultrafast anisotropy decay presents a spectral signature that reveals contrasting energy pathways in different chlorosomes.

• Ledum, Morten; Carrer, Manuel; Sen, Samiran; Li, Xinmeng; Cascella, Michele & Bore, Sigbjørn Løland (2023). HylleraasMD: Massively parallel hybrid particle-field molecular dynamics in Python. Journal of Open Source Software (JOSS). 8(84). doi: 10.21105/joss.04149. Full text in Research Archive Show summary

  Molecular dynamics (MD) is a computational methodology in which the dynamical behavior of systems of interacting atoms and molecules is investigated by integrating the corresponding classical equations of motion. The analysis of the molecular trajectories yields an incredibly powerful computational microscope with atomic resolution. While prominent examples of molecular dynamics involving all-atom models exist, many systems operate on time- and lengths scales too large, precluding the use of such an approach. The intrinsic complexity of biological soft-matter systems has necessitated the development of coarse-grained (CG) MD models wherein groups of atoms are treated as individual entities. To probe experimentally relevant length- (nm–μm) and time- (ps–ms) scales, further reduction of computational complexity may be warranted through the removal of explicit particle–particle interactions in favor of particle–density field interactions. Such hybrid particle–field (hPF) models recast the interactions between particle pairs into a system of free particles interacting with an external potential dependent on the density, in analogy with self-consistent field theories. HylleraasMD (named after our affiliate centre, the Hylleraas Centre for Quantum Molecular Sciences) (HyMD) is a Python package capable of highly parallel hPF-MD simulations of a wide range of surfactants and other biological systems in a CG representation. At present, it is the only open-source implementation of the hPF formalism freely available to computational researchers.

• Erić, Vesna; Li, Xinmeng; Dsouza, Lolita; Frehan, Sean K.; Huijser, Annemarie & Holzwarth, Alfred R. [Show all 10 contributors for this article] (2022). Manifestation of Hydrogen Bonding and Exciton Delocalization on the Absorption and Two-Dimensional Electronic Spectra of Chlorosomes. Journal of Physical Chemistry B. ISSN 1520-6106. doi: 10.1021/acs.jpcb.2c07143. Full text in Research Archive Show summary

  Chlorosomes are supramolecular aggregates that contain thousands of bacteriochlorophyll molecules. They perform the most efficient ultrafast excitation energy transfer of all natural light-harvesting complexes. Their broad absorption band optimizes light capture. In this study, we identify the microscopic sources of the disorder causing the spectral width and reveal how it affects the excited state properties and the optical response of the system. We combine molecular dynamics, quantum chemical calculations, and response function calculations to achieve this goal. The predicted linear and two-dimensional electronic spectra are found to compare well with experimental data reproducing all key spectral features. Our analysis of the microscopic model reveals the interplay of static and dynamic disorder from the molecular perspective. We find that hydrogen bonding motifs are essential for a correct description of the spectral line shape. Furthermore, we find that exciton delocalization over tens to hundreds of molecules is consistent with the two-dimensional electronic spectra.

• Li, Xinmeng; Buda, Francesco; Groot, Huub de & Sevink, G.J.Agur (2022). The role of chirality and plastic crystallinity in the optical and mechanical properties of chlorosomes. iScience. doi: 10.1016/j.isci.2021.103618. Full text in Research Archive Show summary

  The most efficient light-harvesting antennae found in nature, chlorosomes, are molecular tubular aggregates (TMAs) assembled by pigments without protein scaffolds. Here, we discuss a classification of chlorosomes as a unique tubular plastic crystal and we attribute the robust energy transfer in chlorosomes to this unique nature. To systematically study the role of supramolecular tube chirality by molecular simulation, a role that has remained unresolved, we share a protocol for generating realistic tubes at atomic resolution. We find that both the optical and the mechanical behavior are strongly dependent on chirality. The optical-chirality relation enables a direct interpretation of experimental spectra in terms of overall tube chirality. The mechanical response shows that the overall chirality regulates the hardness of the tube and provides a new characteristic for relating chlorosomes to distinct chirality. Our protocol also applies to other TMA systems and will inspire other systematic studies beyond lattice models.

• Sevink, G.J.A.; Blokhuis, Edgar M.; Li, Xinmeng & Milano, Giuseppe (2020). Efficient and realistic simulation of phase coexistence. Journal of Chemical Physics. ISSN 0021-9606. 153(24). doi: 10.1063/5.0027778. Full text in Research Archive Show summary

  We show how an existing concurrent multi-scale method named hybrid particle field-molecular dynamics (hPF-MD) can be adapted to enable the simulation of structure and/or structural dynamics in compressible systems. Implementing such new equations of state (EOS) into hPF-MD, while conserving the efficiency associated with treating intermolecular interactions in a continuum fashion, opens this method up to describe a new class of phenomena in which non-uniform densities play a role, for example, evaporation and crystallization. We carefully consider how compressible hPF-MD compares to its mean-field counterpart for two particular EOS, adopted from the Cell Model for polymers and the Carnahan–Starling expression for hard spheres. Here, we performed a very basic analysis for a single-component system, focusing on the significance of various particle-based parameters and the particle-to-field projection. Our results illustrate the key role of the particle density per field grid cell and show that projection based on a Gaussian kernel is preferred over the standard cloud-in-cell projection. They also suggest that the behavior of hPF-MD close to the critical point is non-classical, i.e., in agreement with a critical exponent for a pure particle description, despite the mean-field origin of the method.

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