Dataset Information

Coarse-grained model for simulation of RNA three-dimensional structures.

ABSTRACT: The accurate prediction of an RNA's three-dimensional structure from its "primary structure" will have a tremendous influence on the experimental design and its interpretation and ultimately our understanding of the many functions of RNA. This paper presents a general coarse-grained (CG) potential for modeling RNA 3-D structures. Each nucleotide is represented by five pseudo atoms, two for the backbone (one for the phosphate and another for the sugar) and three for the base to represent base-stacking interactions. The CG potential has been parametrized from statistical analysis of 688 RNA experimental structures. Molecular dynamic simulations of 15 RNA molecules with the length of 12-27 nucleotides have been performed using the CG potential, with performance comparable to that from all-atom simulations. For ~75% of systems tested, simulated annealing led to native-like structures at least once out of multiple repeated runs. Furthermore, with weak distance restraints based on the knowledge of three to five canonical Watson-Crick pairs, all 15 RNAs tested are successfully folded to within 6.5 Å of native structures using the CG potential and simulated annealing. The results reveal that with a limited secondary structure model the current CG potential can reliably predict the 3-D structures for small RNA molecules. We also explored an all-atom force field to construct atomic structures from the CG simulations.

SUBMITTER: Xia Z

PROVIDER: S-EPMC2989335 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Coarse-grained model for simulation of RNA three-dimensional structures.

Xia Zhen Z Gardner David Paul DP Gutell Robin R RR Ren Pengyu P

The journal of physical chemistry. B 20101001 42

The accurate prediction of an RNA's three-dimensional structure from its "primary structure" will have a tremendous influence on the experimental design and its interpretation and ultimately our understanding of the many functions of RNA. This paper presents a general coarse-grained (CG) potential for modeling RNA 3-D structures. Each nucleotide is represented by five pseudo atoms, two for the backbone (one for the phosphate and another for the sugar) and three for the base to represent base-sta ...[more]

PMID: 20883011

Similar Datasets

Project description:Using both atomistic and coarse-grained (CG) models, we compute the three-dimensional stress field around a gramicidin A (gA) dimer in lipid bilayers that feature different degrees of negative hydrophobic mismatch. The general trends in the computed stress field are similar at the atomistic and CG levels, supporting the use of the CG model for analyzing the mechanical features of protein/lipid/water interfaces. The calculations reveal that the stress field near the protein-lipid interface exhibits a layered structure with both significant repulsive and attractive regions, with the magnitude of the stress reaching 1000 bar in certain regions. Analysis of density profiles and stress field distributions helps highlight the Trp residues at the protein/membrane/water interface as mechanical anchors, suggesting that similar analysis is useful for identifying tension sensors in other membrane proteins, especially membrane proteins involved in mechanosensation. This work fosters a connection between microscopic and continuum mechanics models for proteins in complex environments and makes it possible to test the validity of assumptions commonly made in continuum mechanics models for membrane mediated processes. For example, using the calculated stress field, we estimate the free energy of membrane deformation induced by the hydrophobic mismatch, and the results for regions beyond the annular lipids are in general consistent with relevant experimental data and previous theoretical estimates using elasticity theory. On the other hand, the assumptions of homogeneous material properties for the membrane and a bilayer thickness at the protein/lipid interface being independent of lipid type (e.g., tail length) appear to be oversimplified, highlighting the importance of annular lipids of membrane proteins. Finally, the stress field analysis makes it clear that the effect of even rather severe hydrophobic mismatch propagates to only about two to three lipid layers, thus putting a limit on the range of cooperativity between membrane proteins in crowded cellular membranes.

Project description:Disordered proteins and nucleic acids can condense into droplets that resemble the membraneless organelles observed in living cells. MD simulations offer a unique tool to characterize the molecular interactions governing the formation of these biomolecular condensates, their physicochemical properties, and the factors controlling their composition and size. However, biopolymer condensation depends sensitively on the balance between different energetic and entropic contributions. Here, we develop a general strategy to fine-tune the potential energy function for molecular dynamics simulations of biopolymer phase separation. We rebalance protein-protein interactions against solvation and entropic contributions to match the excess free energy of transferring proteins between dilute solution and condensate. We illustrate this formalism by simulating liquid droplet formation of the FUS low-complexity domain (LCD) with a rebalanced MARTINI model. By scaling the strength of the nonbonded interactions in the coarse-grained MARTINI potential energy function, we map out a phase diagram in the plane of protein concentration and interaction strength. Above a critical scaling factor of αc ≈ 0.6, FUS-LCD condensation is observed, where α = 1 and 0 correspond to full and repulsive interactions in the MARTINI model. For a scaling factor α = 0.65, we recover experimental densities of the dilute and dense phases, and thus the excess protein transfer free energy into the droplet and the saturation concentration where FUS-LCD condenses. In the region of phase separation, we simulate FUS-LCD droplets of four different sizes in stable equilibrium with the dilute phase and slabs of condensed FUS-LCD for tens of microseconds, and over one millisecond in aggregate. We determine surface tensions in the range of 0.01-0.4 mN/m from the fluctuations of the droplet shape and from the capillary-wave-like broadening of the interface between the two phases. From the dynamics of the protein end-to-end distance, we estimate shear viscosities from 0.001 to 0.02 Pa s for the FUS-LCD droplets with scaling factors α in the range of 0.625-0.75, where we observe liquid droplets. Significant hydration of the interior of the droplets keeps the proteins mobile and the droplets fluid.

Dataset Information

Coarse-grained model for simulation of RNA three-dimensional structures.

Publications

Coarse-grained model for simulation of RNA three-dimensional structures.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets