To model large biomolecular systems, such as cell and organelles an atomistic description is not currently achievable and is not generally practical. Therefore, simplified coarse-grained (CG) modelling becomes a necessity. One of the most important cellular components is chromatin, a large DNA-protein complex where DNA is highly compacted. Recent progress in coarse graining modelling of the major chromatin components, double helical DNA and the nucleosome core particle (NCP) is presented. First, general principles and approaches allowing rigorous bottom-to-top generation of interaction potentials in the CG models are presented. Then, recent CG models of DNA are reviewed and their adequacy is benchmarked against experimental data on the salt dependence of DNA flexibility (persistence length). Furthermore, a few recent CG models of the NCP are described and their application for studying salt-dependent NCP-NCP interaction is discussed. An example of a multiscale approach to CG modelling of chromatin is presented where interactions and self-assembly of thousands of NCPs in solution are observed.
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http://dx.doi.org/10.1016/j.cis.2016.02.002 | DOI Listing |
Life (Basel)
January 2025
Chemistry Department, Lomonosov Moscow State University, 119991 Moscow, Russia.
Inorganic pyrophosphatases, or PPases, are ubiquitous enzymes whose activity is necessary for a large number of biosynthetic reactions. The catalytic function of PPases is dependent on certain conformational changes that have been previously characterized based on the comparison of the crystal structures of various complexes. The current work describes the conformational dynamics of a structural model of human mitochondrial pyrophosphatase hPPA2 using molecular dynamics simulation, all-atom principal component analysis, and coarse-grained normal mode analysis.
View Article and Find Full Text PDFEntropy (Basel)
January 2025
Computational Neuroscience Group, Universitat Pompeu Fabra, 08005 Barcelona, Spain.
In the Kolmogorov Theory of Consciousness, algorithmic agents utilize inferred compressive models to track coarse-grained data produced by simplified world models, capturing regularities that structure subjective experience and guide action planning. Here, we study the dynamical aspects of this framework by examining how the requirement of tracking natural data drives the structural and dynamical properties of the agent. We first formalize the notion of a using the language of symmetry from group theory, specifically employing Lie pseudogroups to describe the continuous transformations that characterize invariance in natural data.
View Article and Find Full Text PDFJ Chem Theory Comput
January 2025
Faculty of Chemistry, University of Gdańsk, Fahrenheit Union of Universities, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland.
Time-averaged restraints from nuclear magnetic resonance (NMR) measurements have been implemented in the UNRES coarse-grained model of polypeptide chains in order to develop a tool for data-assisted modeling of the conformational ensembles of multistate proteins, intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs), many of which are essential in cell biology. A numerically stable variant of molecular dynamics with time-averaged restraints has been introduced, in which the total energy is conserved in sections of a trajectory in microcanonical runs, the bath temperature is maintained in canonical runs, and the time-average-restraint-force components are scaled up with the length of the memory window so that the restraints affect the simulated structures. The new approach restores the conformational ensembles used to generate ensemble-averaged distances, as demonstrated with synthetic restraints.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai, 201210, China.
3D disordered fibrous network structures (3D-DFNS), such as cytoskeletons, collagen matrices, and spider webs, exhibit remarkable material efficiency, lightweight properties, and mechanical adaptability. Despite their widespread in nature, the integration into engineered materials is limited by the lack of study on their complex architectures. This study addresses the challenge by investigating the structure-property relationships and stability of biomimetic 3D-DFNS using large datasets generated through procedural modeling, coarse-grained molecular dynamics simulations, and machine learning.
View Article and Find Full Text PDFCarbohydr Polym
March 2025
Department of Chemistry, Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, USA; Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA 24061, USA. Electronic address:
Combining polysaccharides with polypeptides enables growth of diverse nanostructures with minimal toxicity, low immune response, and potential biodegradability. However, examples of nanostructures combining polysaccharides with polypeptides are limited due to synthetic difficulties and related issues of solubility, purification, and characterization, with previous reports of polysaccharide-block-polypeptide block copolymers requiring methods such as polymer-polymer coupling and post-polymerization modifications paired with difficult purification steps. Here, we synthesized dextran-block-poly(benzyl glutamate) block copolymers in water via polymerization-induced self-assembly (PISA) to form nanostructures in situ, studying their morphologies using experimental methods and molecular modeling.
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