The Martini coarse-grained force field has been successfully used for simulating a wide range of (bio)molecular systems. Recent progress in our ability to test the model against fully atomistic force fields, however, has revealed some shortcomings. Most notable, phenylalanine and proline were too hydrophobic, and dimers formed by polar residues in apolar solvents did not bind strongly enough. Here, we reparametrize these residues either through reassignment of particle types or by introducing embedded charges. The new parameters are tested with respect to partitioning across a lipid bilayer, membrane binding of Wimley-White peptides, and dimerization free energy in solvents of different polarity. In addition, we improve some of the bonded terms in the Martini protein force field that lead to a more realistic length of α-helices and to improved numerical stability for polyalanine and glycine repeats. The new parameter set is denoted Martini version 2.2.
Computational modeling of biological systems is challenging because of the multitude of spatial and temporal scales involved. Replacing atomistic detail with lower resolution, coarse grained (CG), beads has opened the way to simulate large-scale biomolecular processes on time scales inaccessible to all-atom models. We provide an overview of some of the more popular CG models used in biomolecular applications to date, focusing on models that retain chemical specificity. A few state-of-the-art examples of protein folding, membrane protein gating and self-assembly, DNA hybridization, and modeling of carbohydrate fibers are used to illustrate the power and diversity of current CG modeling.
A wide
variety of phytochemicals are consumed for their perceived
health benefits. Many of these phytochemicals have been found to alter
numerous cell functions, but the mechanisms underlying their biological
activity tend to be poorly understood. Phenolic phytochemicals are
particularly promiscuous modifiers of membrane protein function, suggesting
that some of their actions may be due to a common, membrane bilayer-mediated
mechanism. To test whether bilayer perturbation may underlie this
diversity of actions, we examined five bioactive phenols reported
to have medicinal value: capsaicin from chili peppers, curcumin from
turmeric, EGCG from green tea, genistein from soybeans, and resveratrol
from grapes. We find that each of these widely consumed phytochemicals
alters lipid bilayer properties and the function of diverse membrane
proteins. Molecular dynamics simulations show that these phytochemicals
modify bilayer properties by localizing to the bilayer/solution interface.
Bilayer-modifying propensity was verified using a gramicidin-based
assay, and indiscriminate modulation of membrane protein function
was demonstrated using four proteins: membrane-anchored metalloproteases,
mechanosensitive ion channels, and voltage-dependent potassium and
sodium channels. Each protein exhibited similar responses to multiple
phytochemicals, consistent with a common, bilayer-mediated mechanism.
Our results suggest that many effects of amphiphilic phytochemicals
are due to cell membrane perturbations, rather than specific protein
binding.
Coarse-grained (CG) models allow simulation of larger systems for longer times by decreasing the number of degrees of freedom compared with all-atom models. Here we introduce an implicit-solvent version of the popular CG Martini model, nicknamed "Dry" Martini. To account for the omitted solvent degrees of freedom, the nonbonded interaction matrix underlying the Martini force field was reparametrized. The Dry Martini force field reproduces relatively well a variety of lipid membrane properties such as area per lipid, bilayer thickness, bending modulus, and coexistence of liquid-ordered and disordered domains. Furthermore, we show that the new model can be applied to study membrane fusion and tether formation, with results similar to those of the standard Martini model. Membrane proteins can also be included, but less quantitative results are obtained. The absence of water in Dry Martini leads to a significant speedup for large systems, opening the way to the study of complex multicomponent membranes containing millions of lipids.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.