A Practical View of the Martini Force Field

Bruininks, Bart Marlon Herwig; Souza, Paulo C. T.; Marrink, Siewert J.

doi:10.1007/978-1-4939-9608-7_5

Cited by 40 publications

(41 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation indicates that the current parameterization of the Martini force field causes too compact structures for the flexible protein TIA-1. We speculate that this may be ascribed to the protein-protein interactions between domains of TIA-1 being too attractive, as such protein "stickiness" has previously been observed for simulations in Martini v2.2 (39,(49)(50)(51), and Martini v.3.0.beta.3.2 (3). We considered other reasons for the poor fits, including the fact that we keep domains fixed with elastic networks, and limited accuracy of the calculated SAXS data, but none of these could easily explain the large discrepancy between data and calculated scattering from the unperturbed ensemble.…”

Section: An MD Simulation With the Coarse-grained Martini Model Does mentioning

confidence: 80%

Combining molecular dynamics simulations with small-angle X-ray and neutron scattering data to study multi-domain proteins in solution

Larsen

Wang²,

Bottaro

et al. 2019

Preprint

View full text Add to dashboard Cite

AbstractMany proteins contain multiple folded domains separated by flexible linkers, and the ability to describe the structure and conformational heterogeneity of such flexible systems pushes the limits of structural biology. Using the three-domain protein TIA-1 as an example, we here combine coarse-grained molecular dynamics simulations with previously measured small-angle scattering data to study the conformation of TIA-1 in solution. We show that while the coarse-grained potential (Martini) in itself leads to too compact conformations, increasing the strength of protein-water interactions results in ensembles that are in very good agreement with experiments. We show how these ensembles can be refined further using a Bayesian/Maximum Entropy approach, and examine the robustness to errors in the energy function. In particular we find that as long as the initial simulation is relatively good, reweighting against experiments is very robust. We also study the relative information in X-ray and neutron scattering experiments and find that refining against the SAXS experiments leads to improvement in the SANS data. Our results suggest a general strategy for studying the conformation of multi-domain proteins in solution that combines coarse-grained simulations with small-angle X-ray scattering data that are generally most easy to obtain. These results may in turn be used to design further small-angle neutron scattering experiments that exploit contrast variation through 1H/2H isotope substitutions.

show abstract

Section: An MD Simulation With the Coarse-grained Martini Model Does mentioning

confidence: 80%

Combining molecular dynamics simulations with small-angle X-ray and neutron scattering data to study multi-domain proteins in solution

Larsen

Wang²,

Bottaro

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…12 The Martini force field is the most widely used for the CG representation of biomolecular systems. 13,14 Martini has been successfully applied in a variety of studies including membrane reorganization, transmembrane oligomerization, nanoparticle self-assembly and many others. [15][16][17][18][19] Until recently, however, only a few applications of Martini force field to investigate proteinprotein interactions in aqueous solution appeared in the literature, 20 perhaps owing to the fact that Martini may overestimate protein-protein associations in water 21 and in some cases also in membranes.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the Efficiency of the Martini Force Field to Study Protein Dimerization in Aqueous and Membrane Environments

Lamprakis

Andreadelis

Manchester³

et al. 2021

J. Chem. Theory Comput.

View full text Add to dashboard Cite

Protein-protein complex assembly is one of the major drivers of biological response. Understanding the mechanisms of protein oligomerization/dimerization would allow one to elucidate how these complexes participate in biological activities and could ultimately lead to new approaches in designing novel therapeutic agents. However, determining the exact association pathways and structures of such complexes remains a challenge. Here, we use parallel tempering metadynamics simulations in the well-tempered ensemble to evaluate the performance of Martini 2.2P and Martini open-beta 3 (Martini 3) force fields in reproducing the structure and energetics of the dimerization process of membrane proteins and proteins in an aqueous solution in reasonable accuracy and throughput. We find that Martini 2.2P systematically overestimates the free energy of association by estimating large barriers in distinct areas, which likely leads to overaggregation when multiple monomers are present. In comparison, the less viscous Martini 3 results in a systematic underestimation of the free energy of association for proteins in solution, while it performs well in describing the association of membrane proteins. In all cases the near-native dimer complexes are identified as minima in the free energy surface albeit not always as the lowest minima. In the case of Martini 3 we find that the spurious supramolecular protein aggregation present in Martini 2.2P multimer simulations is alleviated and thus this force field may be more suitable for the study of protein oligomerization. We propose that the use of enhanced sampling simulations with a refined coarse-grained force field and appropriately defined collective variables is a robust approach for studying the protein dimerization process, although one should be cautious of the ranking of energy minima. File list (2) download file view on ChemRxiv Protein-Dimerization-MARTINI.pdf (3.46 MiB) download file view on ChemRxiv SUPPORTING INFORMATION_martini-dimerization.pdf (8.58 MiB)

show abstract

“…This has often required high concentration of nanostructure and the application of external voltage [19,116]. The required energy for insertion can be estimated using coarse-grained models such as MARTINI force field, developed to simulate lipid bilayers and their interactions with a range of biomolecular structures [117,118]. Using modelling and all atom simulations, the free energy gain from the insertion of a cholesterol can be predicted [119].…”

Section: Challenges and Future Directions Of Membrane-spanning Dna Namentioning

confidence: 99%

The Fusion of Lipid and DNA Nanotechnology

Darley

Singh

Surace

et al. 2019

Genes

View full text Add to dashboard Cite

Lipid membranes form the boundary of many biological compartments, including organelles and cells. Consisting of two leaflets of amphipathic molecules, the bilayer membrane forms an impermeable barrier to ions and small molecules. Controlled transport of molecules across lipid membranes is a fundamental biological process that is facilitated by a diverse range of membrane proteins, including ion-channels and pores. However, biological membranes and their associated proteins are challenging to experimentally characterize. These challenges have motivated recent advances in nanotechnology towards building and manipulating synthetic lipid systems. Liposomes—aqueous droplets enclosed by a bilayer membrane—can be synthesised in vitro and used as a synthetic model for the cell membrane. In DNA nanotechnology, DNA is used as programmable building material for self-assembling biocompatible nanostructures. DNA nanostructures can be functionalised with hydrophobic chemical modifications, which bind to or bridge lipid membranes. Here, we review approaches that combine techniques from lipid and DNA nanotechnology to engineer the topography, permeability, and surface interactions of membranes, and to direct the fusion and formation of liposomes. These approaches have been used to study the properties of membrane proteins, to build biosensors, and as a pathway towards assembling synthetic multicellular systems.

show abstract

A Practical View of the Martini Force Field

Cited by 40 publications

References 61 publications

Combining molecular dynamics simulations with small-angle X-ray and neutron scattering data to study multi-domain proteins in solution

Combining molecular dynamics simulations with small-angle X-ray and neutron scattering data to study multi-domain proteins in solution

Evaluating the Efficiency of the Martini Force Field to Study Protein Dimerization in Aqueous and Membrane Environments

The Fusion of Lipid and DNA Nanotechnology

Contact Info

Product

Resources

About