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1. A hybrid approach for coarse-graining helical peptoids: Solvation, secondary structure, and assembly

   https://doi.org/10.1063/5.0138510  

   Banerjee, Akash; Dutt, Meenakshi (March 2023, The Journal of Chemical Physics)

   Protein mimics such as peptoids form self-assembled nanostructures whose shape and function are governed by the side chain chemistry and secondary structure. Experiments have shown that a peptoid sequence with a helical secondary structure assembles into microspheres that are stable under various conditions. The conformation and organization of the peptoids within the assemblies remains unknown and is elucidated in this study via a hybrid, bottom-up coarse-graining approach. The resultant coarse-grained (CG) model preserves the chemical and structural details that are critical for capturing the secondary structure of the peptoid. The CG model accurately captures the overall conformation and solvation of the peptoids in an aqueous solution. Furthermore, the model resolves the assembly of multiple peptoids into a hemispherical aggregate that is in qualitative agreement with the corresponding results from experiments. The mildly hydrophilic peptoid residues are placed along the curved interface of the aggregate. The composition of the residues on the exterior of the aggregate is determined by two conformations adopted by the peptoid chains. Hence, the CG model simultaneously captures sequence-specific features and the assembly of a large number of peptoids. This multiscale, multiresolution coarse-graining approach could help in predicting the organization and packing of other tunable oligomeric sequences of relevance to biomedicine and electronics. 

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2. Using classifiers to understand coarse-grained models and their fidelity with the underlying all-atom systems

   https://doi.org/10.1063/5.0146812  

   Durumeric, Aleksander_E P; Voth, Gregory A (June 2023, The Journal of Chemical Physics)

   Bottom-up coarse-grained (CG) molecular dynamics models are parameterized using complex effective Hamiltonians. These models are typically optimized to approximate high dimensional data from atomistic simulations. However, human validation of these models is often limited to low dimensional statistics that do not necessarily differentiate between the CG model and said atomistic simulations. We propose that classification can be used to variationally estimate high dimensional error and that explainable machine learning can help convey this information to scientists. This approach is demonstrated using Shapley additive explanations and two CG protein models. This framework may also be valuable for ascertaining whether allosteric effects at the atomistic level are accurately propagated to a CG model. 

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3. Understanding dynamics in coarse-grained models. I. Universal excess entropy scaling relationship

   https://doi.org/10.1063/5.0116299  

   Jin, Jaehyeok; Schweizer, Kenneth S.; Voth, Gregory A. (January 2023, The Journal of Chemical Physics)

   Coarse-grained (CG) models facilitate an efficient exploration of complex systems by reducing the unnecessary degrees of freedom of the fine-grained (FG) system while recapitulating major structural correlations. Unlike structural properties, assessing dynamic properties in CG modeling is often unfeasible due to the accelerated dynamics of the CG models, which allows for more efficient structural sampling. Therefore, the ultimate goal of the present series of articles is to establish a better correspondence between the FG and CG dynamics. To assess and compare dynamical properties in the FG and the corresponding CG models, we utilize the excess entropy scaling relationship. For Paper I of this series, we provide evidence that the FG and the corresponding CG counterpart follow the same universal scaling relationship. By carefully reviewing and examining the literature, we develop a new theory to calculate excess entropies for the FG and CG systems while accounting for entropy representability. We demonstrate that the excess entropy scaling idea can be readily applied to liquid water and methanol systems at both the FG and CG resolutions. For both liquids, we reveal that the scaling exponents remain unchanged from the coarse-graining process, indicating that the scaling behavior is universal for the same underlying molecular systems. Combining this finding with the concept of mapping entropy in CG models, we show that the missing entropy plays an important role in accelerating the CG dynamics. 

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4. A hybrid coarse-grained model for structure, solvation and assembly of lipid-like peptides

   https://doi.org/10.1039/D1CP04205J  

   Banerjee, Akash; Lu, Chien Yu; Dutt, Meenakshi (January 2022, Physical Chemistry Chemical Physics)

   Reconstituted photosynthetic proteins which are activated upon exposure to solar energy hold enormous potential for powering future solid state devices and solar cells. The functionality and integration of these proteins into such devices has been successfully enabled by lipid-like peptides. Yet, a fundamental understanding of the organization of these peptides with respect to the photosynthetic proteins and themselves remains unknown and is critical for guiding the design of such light-activated devices. This study investigates the relative organization of one such peptide sequence V 6 K 2 (V: valine and K: lysine) within assemblies. Given the expansive spatiotemporal scales associated with this study, a hybrid coarse-grained (CG) model which captures the structure, conformation and aggregation of the peptide is adopted. The CG model uses a combination of iterative Boltzmann inversion and force matching to provide insight into the relative organization of V 6 K 2 in assemblies. The CG model reproduces the structure of a V 6 K 2 peptide sequence along with its all atom (AA) solvation structure. The relative organization of multiple peptides in an assembly, as captured by CG simulations, is in agreement with corresponding results from AA simulations. Also, a backmapping procedure reintroduces the AA details of the peptides within the aggregates captured by the CG model to demonstrate the relative organization of the peptides. Furthermore, a large number of peptides self-assemble into an elongated micelle in the CG simulation, which is consistent with experimental findings. The coarse-graining procedure is tested for transferability to longer peptide sequences, and hence can be extended to other amphiphilic peptide sequences. 

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5. Everything You Want to Know About Coarse‐Graining and Never Dared to Ask: Macromolecules as a Key Example

   https://doi.org/10.1002/wcms.70022  

   Guenza, Marina_G (April 2025, WIREs Computational Molecular Science)

   ABSTRACT Coarse‐graining (CG) is transforming the study of molecular systems, allowing researchers to explore by computer simulations larger and more complex structures than ever before. Continued advancements in CG techniques are making simulations more efficient, establishing this approach as a cornerstone for designing innovative materials and eco‐friendly alternatives to traditional plastics. Additionally, CG methods are becoming indispensable for unraveling the complexities and functional mechanisms of large‐scale macromolecular machines within cells. Yet, crafting an effective coarse‐grained model demands a nuanced understanding of its advantages and limitations. Faster simulations come at the cost of molecular detail and accuracy in some properties, so that it is essential to balance computational efficiency with the specific needs of the system one wants to simulate. By asking the right questions, researchers can select models that offer the desired benefits while managing trade‐offs. This article delves into the potential of different CG models and the compromises inherent in their adoption, highlighting their role in shaping the future of material science and biophysics. 

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