Modeling DMPC lipid membranes with SIRAH force-field

Abstract

Coarse-grained simulation schemes are increasingly gaining popularity in the scientific community because of the significant speed up granted, allowing a considerable expansion of the accessible time and size scales accessible to molecular simulations. However, the number of compatible force fields capable of representing ensembles containing different molecular species (i.e., Protein, DNA, etc) is still limited. Here, we present a set of parameters and simplified representation for lipids compatible with the SIRAH force field for coarse-grained simulations ( http://www.sirahff.com ). We show that the present model not only achieves a correct reproduction of structural parameters as area per lipid and thickness, but also dynamic descriptors such as diffusion coefficient, order parameters, and proper temperature driven variations. Adding phospholipid membranes to the existing aqueous solution, protein and DNA representations of the SIRAH force field permit considering the most common problems tackled by the biomolecular simulation community.

The SIRAH force field 2.0: Altius, Fortius, Citius

“…Nevertheless, calculation of the total number of contacts remained nearly constant, experiencing a slight increase with sizable oscillations ( Figure 4D). The average number of inter C contacts was 58 over the last 100 ns, which is comparable to the initial value of 51, indicating that the protein-protein interface was maintained [16][17][18][19][20][21][22][23][24][25][26][27][28] despite the loss in specificity. A stringent control for this system was the coordination of Ca 2+ ions.…”

“…Although a universal recipe for parameter development is not available on SIRAH, the physicochemical vision of beads based on functional groups provided in Figure 2 will facilitate the development of a higher number of molecules, enriching the biological diversity amenable to be studied with SIRAH. Indeed, parameters for CG glycans, metallic ions and different phospholipids [21][22][23][24][25][26][27][28] compatible with this protein force field are currently being tested. These sets of new interaction parameters will offer in the near future the possibility to address highly complex systems containing glycosylated and metallo-proteins, polysaccharides, membranes and nucleic acids.…”

Protein structure prediction and design in a biologically-realistic implicit membrane

“…With current technology, detailed all-atom models can be used to explore membrane dynamics for hundreds of nanoseconds (18): the time scale required to achieve equilibrated properties on a bilayer with approximately 250 lipids (19). Coarse-grained representations such as MARTINI (20), ELBA (21), and SIRAH (22) reduce computation time by mapping atoms onto representative beads. As a result, simulations have explored dynamics up to the millisecond time scale to access features of membrane organization and large protein domain motions (23).…”

Computer simulations of protein–membrane systems

“…Some of the other popular CG-FFs available for simulation of membrane lipids include the SDK (named after its developers Shinoda-DeVane-Klein) FF, 93 later extended as SPICA FF, 183 the ELBA (stands for electrostatic-based) FF, 184 the SIRAH FF, 185 and the UNRES FF 186 (see also chapter "Scale-consistent approach to the derivation of coarse-grained force fields for simulating structure, dynamics, and thermodynamics of biopolymers" by Liwo of this book). The SDK CG lipid FF was originally developed for the study of surfactants and zwitterionic lipids.…”

“…The SIRAH FF is based on a top-down philosophy that aims to correctly reproduce lipid thickness and area per lipid among other membrane properties. 185…”