Multi-scale simulations of biological systems using the OPEP coarse-grained model

Sterpone, Fabio; Doutreligne, Sébastien; Tran, Thanh Thuy; Melchionna, Simone; Baaden, Marc; Nguyen, Phuong H.; Derreumaux, Philippe

doi:10.1016/j.bbrc.2017.08.165

Cited by 28 publications

(33 citation statements)

References 97 publications

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“…The combination of steered MD (sMD) simulations and atomic force microscopy (AFM) measurements allowed to get insight into the molecular origin of the conformational change [ 54 , 55 , 56 ]. Moreover, using the fimbrial tip (consisting of FimH, FimG followed by one FimF) structure [ 57 ], a coarse-grained lattice Boltzmann MD simulation study showed that the application of fluid flow leads to a drastic alternation of the complex conformation [ 58 ]. In these simulations, the chain stretched according to the fluid velocity drag in accordance with a shear-force dependent conformational change.…”

Section: The Molecular Binding Mechanism Of Small Mannosidic Compomentioning

confidence: 99%

Targeting Dynamical Binding Processes in the Design of Non-Antibiotic Anti-Adhesives by Molecular Simulation—The Example of FimH

et al. 2018

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Located at the tip of type I fimbria of Escherichia coli, the bacterial adhesin FimH is responsible for the attachment of the bacteria to the (human) host by specifically binding to highly-mannosylated glycoproteins located on the exterior of the host cell wall. Adhesion represents a necessary early step in bacterial infection and specific inhibition of this process represents a valuable alternative pathway to antibiotic treatments, as such anti-adhesive drugs are non-intrusive and are therefore unlikely to induce bacterial resistance. The currently available anti-adhesives with the highest affinities for FimH still feature affinities in the nanomolar range. A prerequisite to develop higher-affinity FimH inhibitors is a molecular understanding of the FimH-inhibitor complex formation. The latest insights in the formation process are achieved by combining several molecular simulation and traditional experimental techniques. This review summarizes how molecular simulation contributed to the current knowledge of the molecular function of FimH and the importance of dynamics in the inhibitor binding process, and highlights the importance of the incorporation of dynamical aspects in (future) drug-design studies.

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Section: The Molecular Binding Mechanism Of Small Mannosidic Compomentioning

confidence: 99%

Targeting Dynamical Binding Processes in the Design of Non-Antibiotic Anti-Adhesives by Molecular Simulation—The Example of FimH

et al. 2018

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“…It is a model with representation of backbone as all-atom and side chains as a single bead with an exception of proline represented by three beads. The development and rise of the OPEP model have been reviewed earlier by Fabio Sterpone et al [105]. This model has been used for protein folding, aggregation studies, role of hydrodynamics in peptide aggregation and modeling of protein structure.…”

Section: Opep (Optimized Potential For Efficient Structure Prediction)mentioning

confidence: 99%

“…The hydrodynamic interaction effect was studied and found to enhance the aggregation process [106]. In another work, the OPEP model has been implied to study the amyloid fibril formation along with interactive simulations for peptide folding and response to mechanical stress caused by the surrounding fluid by catch bond proteins [105]. In a similar subject of an amylin oligomer study, the OPEP model was coupled with replica exchange molecular dynamics to study the mutation effect on its structural and thermodynamic properties [51].…”

Section: Opep (Optimized Potential For Efficient Structure Prediction)mentioning

confidence: 99%

Recent Advances in Coarse-Grained Models for Biomolecules and Their Applications

Singh

2019

IJMS

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Molecular dynamics simulations have emerged as a powerful tool to study biological systems at varied length and timescales. The conventional all-atom molecular dynamics simulations are being used by the wider scientific community in routine to capture the conformational dynamics and local motions. In addition, recent developments in coarse-grained models have opened the way to study the macromolecular complexes for time scales up to milliseconds. In this review, we have discussed the principle, applicability and recent development in coarse-grained models for biological systems. The potential of coarse-grained simulation has been reviewed through state-of-the-art examples of protein folding and structure prediction, self-assembly of complexes, membrane systems and carbohydrates fiber models. The multiscale simulation approaches have also been discussed in the context of their emerging role in unravelling hierarchical level information of biosystems. We conclude this review with the future scope of coarse-grained simulations as a constantly evolving tool to capture the dynamics of biosystems.

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“…Modeling approaches have been widely used to study Alzheimer's, as reviewed in [15,16]. In particular multi-scale and multi-physics simulations may be required to address the sampling and time-scale challenges imposed by the underlying processes [17], with some involved molecules being possibly intrinsically disordered.…”

Section: Moving Towards Mechanismsmentioning

confidence: 99%

Computer Simulations Provide Guidance for Molecular Medicine Through Insights on Dynamics and Mechanisms at the Atomic Scale

Baaden

2019

IFMBE Proceedings

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Computer simulations provide crucial insights and rationales for the design of molecular approaches in medicine. Several case studies illustrate how molecular model building and molecular dynamics simulations of complex molecular assemblies such as membrane proteins help in that process. Important aspects relate to build relevant molecular models with and without a crystal structure, to model membrane aggregates, then to link (dynamic) models to function, and finally to understand key disease-triggering phenomena such as aggregation. Through selected examples-including key signaling pathways in neurotransmission-the links between a molecular-level understanding of biological mechanisms and original approaches to treat disease conditions will be illuminated. Such treatments may be symptomatic, e.g. by better understanding the function and pharmacology of macromolecular key players, or curative, e.g. through molecular inhibition of disease-inducing molecular processes.

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Multi-scale simulations of biological systems using the OPEP coarse-grained model

Cited by 28 publications

References 97 publications

Targeting Dynamical Binding Processes in the Design of Non-Antibiotic Anti-Adhesives by Molecular Simulation—The Example of FimH

Targeting Dynamical Binding Processes in the Design of Non-Antibiotic Anti-Adhesives by Molecular Simulation—The Example of FimH

Recent Advances in Coarse-Grained Models for Biomolecules and Their Applications

Computer Simulations Provide Guidance for Molecular Medicine Through Insights on Dynamics and Mechanisms at the Atomic Scale

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