Dataset Information

Coarse-Grained Simulations of DNA Reveal Angular Dependence of Sticky-End Binding.

ABSTRACT: Annealing between sticky ends of DNA is an intermediate step in ligation. It can also be utilized to program specific binding sites for DNA tile and origami assembly. This reaction is generally understood as a bimolecular reaction dictated by the local concentration of the sticky ends. Its dependence on the relative orientation between the sticky ends, however, is less understood. Here we report on the interactions between DNA sticky ends using the coarse-grained oxDNA model; specifically, we consider how the orientational alignment of the double-stranded DNA (dsDNA) segments affects the time required for the sticky ends to bind, τ_b. We specify the orientation of the dsDNA segments with three parameters: θ, which measures the angle between the helical axes, and ϕ₁ and ϕ₂, which measure rotations of each strand around the helical axis. We find that the binding time depends strongly on both θ and ϕ₂: ∼20-fold change with θ and 10-fold change with ϕ₂. The binding time is the fastest when the helical axes of duplexes are pointing toward each other and the sticky ends protrude from the farthest two points. Our result is relevant for predicting hybridization efficiency of sticky ends that are rotationally restricted.

SUBMITTER: Gravina NM

PROVIDER: S-EPMC8142848 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Coarse-Grained Simulations of DNA Reveal Angular Dependence of Sticky-End Binding.

Gravina Nicholas M NM Gumbart James C JC Kim Harold D HD

The journal of physical chemistry. B 20210419 16

Annealing between sticky ends of DNA is an intermediate step in ligation. It can also be utilized to program specific binding sites for DNA tile and origami assembly. This reaction is generally understood as a bimolecular reaction dictated by the local concentration of the sticky ends. Its dependence on the relative orientation between the sticky ends, however, is less understood. Here we report on the interactions between DNA sticky ends using the coarse-grained oxDNA model; specifically, we co ...[more]

PMID: 33870695

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Project description:We develop coarse-grained models and effective energy functions for simulating thermodynamic and structural properties of multiprotein complexes with relatively low binding affinity (K(d) >1 microM) and apply them to binding of Vps27 to membrane-tethered ubiquitin. Folded protein domains are represented as rigid bodies. The interactions between the domains are treated at the residue level with amino-acid-dependent pair potentials and Debye-Hückel-type electrostatic interactions. Flexible linker peptides connecting rigid protein domains are represented as amino acid beads on a polymer with appropriate stretching, bending, and torsion-angle potentials. In simulations of membrane-attached protein complexes, interactions between amino acids and the membrane are described by residue-dependent short-range potentials and long-range electrostatics. We parameterize the energy functions by fitting the osmotic second virial coefficient of lysozyme and the binding affinity of the ubiquitin-CUE complex. For validation, extensive replica-exchange Monte Carlo simulations are performed of various protein complexes. Binding affinities for these complexes are in good agreement with the experimental data. The simulated structures are clustered on the basis of distance matrices between two proteins and ranked according to cluster population. In approximately 70% of the complexes, the distance root-mean-square is less than 5 A from the experimental structures. In approximately 90% of the complexes, the binding interfaces on both proteins are predicted correctly, and in all other cases at least one interface is correct. Transient and nonspecifically bound structures are also observed. With the validated model, we simulate the interaction between the Vps27 multiprotein complex and a membrane-tethered ubiquitin. Ubiquitin is found to bind preferentially to the two UIM domains of Vps27, but transient interactions between ubiquitin and the VHS and FYVE domains are observed as well. These specific and nonspecific interactions are found to be positively cooperative, resulting in a substantial enhancement of the overall binding affinity beyond the approximately 300 microM of the specific domains. We also find that the interactions between ubiquitin and Vps27 are highly dynamic, with conformational rearrangements enabling binding of Vps27 to diverse targets as part of the multivesicular-body protein-sorting pathway.

Dataset Information

Coarse-Grained Simulations of DNA Reveal Angular Dependence of Sticky-End Binding.

Publications

Coarse-Grained Simulations of DNA Reveal Angular Dependence of Sticky-End Binding.

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