A mesoscale model of DNA is presented (3SPN.1), extending the scheme previously developed by our group. Each nucleotide is mapped onto three interaction sites. Solvent is accounted for implicitly through a medium-effective dielectric constant and electrostatic interactions are treated at the level of Debye-Hückel theory. The force field includes a weak, solvent-induced attraction, which helps mediate the renaturation of DNA. Model parameterization is accomplished through replica exchange molecular dynamics simulations of short oligonucleotide sequences over a range of composition and chain length. The model describes the melting temperature of DNA as a function of composition as well as ionic strength, and is consistent with heat capacity profiles from experiments. The dependence of persistence length on ionic strength is also captured by the force field. The proposed model is used to examine the renaturation of DNA. It is found that a typical renaturation event occurs through a nucleation step, whereby an interplay between repulsive electrostatic interactions and colloidal-like attractions allows the system to undergo a series of rearrangements before complete molecular reassociation occurs.

An analytical description of polymer melts and their mixtures as liquids of interacting soft colloidal particles is obtained from liquid-state theory. The derived center-of-mass pair correlation functions with no adjustable parameters reproduce those computed from united atom molecular dynamics simulations. The coarse-grained description correctly bridges micro-and mesoscopic fluid properties. Molecular dynamics simulations of soft colloidal particles interacting through the calculated effective pair potentials are consistent with data from microscale simulations and analytical formulas.The formulation of an accurate mesoscopic description of macromolecular fluids has been a longstanding goal in polymer physics. Experimentally-relevant polymer dynamics span a wide range of timescales, for which large-scale, long-time properties still depend strongly on the local molecular structure [1]. Pertinent information on structure and dynamics of polymer liquids has been gained from united atom (UA) molecular dynamics (MD) simulations. However, the MD computational time increases as the squared number of interacting units, and the latter has to be large to approximate the thermodynamic limit, rendering an all-atom simulation of long-time polymer dynamics a prohibitive task. One strategy devised to overcome this problem is to renormalize the liquid structure and dynamics using effective-unit coarse-grained descriptions [1]. Specifically, polymers can be described mesoscopically as soft interpenetrating spheres having the overall size of the polymer, i.e., the radius of gyration R g . However, to correctly perform the renormalization procedure, a theoretical framework that bridges properly different lengthscales of interest is needed. Phenomenological mesoscopic potentials were implemented by Dautenhahn and Hall, and later on by Murat and Kremers, to describe polymer melts and blends [2,3]. Hansen and coworkers have recently developed a rigorous numerical description of polymer solutions as liquids of soft interacting colloidal particles [4].In this Letter we start from first-principles liquid-state theory and derive an analytical form of center-of-mass (c.o.m.) pair correlation functions, from which the effective pair soft-core potential acting between molecules in polymer liquids (melts) and their mixtures (blends) is obtained. The c.o.m. pair correlation functions reproduce mesoscale liquid structures obtained from UA-MD simulations [5,6,7] without adjustable parameters. Test systems are polymer melts with different architecture, local semiflexibility, and degree of polymerization (Table I), as well as their mixtures (Table II). Finally, the mesoscopic potential derived by an inversion procedure is used in MD simulations of soft colloidal particles, which reproduce the liquid structure at the level of c.o.m. pair correlation functions.The renormalized pair interaction potential is a function of the c.o.m. total pair correlation function h(r). In reciprocal space,, after a procedure devised by Krakoviack, Hansen, and Loui...

The renaturation/denaturation of DNA oligonucleotides is characterized in the context of expanded ensemble (EXE) and Transition Path Sampling (TPS) simulations. Free energy profiles have been determined from EXE for DNA sequences of varying composition, chain length, and ionic strength. TPS simulations within a Langevin Dynamics formalism have been carried out to obtain further information of the transition state for renaturation. Simulation results reveal that free energy profiles are strikingly similar for the various DNA sequences considered in this work. Taking intact dsDNA to have an extent of reaction ξ = 1.0, the maximum of the free energy profile appears at ξ ≈ 0.15, corresponding to ~2 base pairs. In terms of chain length, the free energy barrier of longer oligonucleotides (30 versus 15 base pairs) is higher and slightly narrower, due to increased sharpness associated with the transition. Low ionic strength tends to decrease free energy barriers, whereby increasing strand rigidity facilitates reassociation. Two mechanisms for DNA reassociation emerge from our analysis of the transition state ensemble. Homogeneous sequences tend to reassociate through a diffusive pathway involving molecular slithering. In contrast, random sequences associate through a more restrictive pathway involving the formation of specific contacts, which then leads to overall molecular zippering. Molecular reassociation in homogeneous sequences appears to be more strongly driven by the relative stability of helix-helix arrangements. In both random and homogeneous sequences, the distribution of contacts suggests that nucleation is favored for sites located within the middle region of the chain. The prevalent extent of reaction for the transition state is ξ ≈ 0.25, and the critical size of the nucleus as obtained from our analysis involves ~4 base pairs.

DNA hybridization plays a central role in biology and, increasingly, in materials science. Yet, there is no precedent for examining the pathways by which specific single-stranded DNA sequences interact to assemble into a double helix. A detailed model of DNA is adopted in this work to examine such pathways and to determine the role of sequence, if any, on DNA hybridization. Transition path sampling simulations reveal that DNA rehybridization is prompted by a distinct nucleation event involving molecular sites with approximately four bases pairing with partners slightly offset from those involved in ideal duplexation. Nucleation is promoted in regions with repetitive base pair sequence motifs, which yield multiple possibilities for finding complementary base partners. Repetitive sequences follow a nonspecific pathway to renaturation consistent with a molecular “slithering” mechanism, whereas random sequences favor a restrictive pathway involving the formation of key base pairs before renaturation fully ensues.

Starting from the Ornstein-Zernike equation the authors derive an analytical theory, at the level of pair correlation functions, which coarse grains polymer melts into liquids of interacting soft colloidal particles. Since it is analytical, the presented coarse-graining approach will be useful in developing multiscale modeling procedures to simulate complex fluids of macromolecules. The accuracy of the theory is tested by its capacity to reproduce the liquid structure, as given by the center-of-mass intermolecular total pair correlation function. The theory is found to agree well with the structure predicted by molecular dynamics simulations of the liquid described at the united atom level as well as by molecular dynamics simulations of the liquid of interacting colloidal particles. The authors perform simulations of the liquid of interacting colloidal particles having as input the potential obtained from their analytical total pair correlation function by enforcing the hypernetted-chain closure approximation. Tests systems are polyethylene melts of chains with increasing degrees of polymerization and polymer melts of chains with different chemical architectures. They also discuss the effect of adopting different conventional approximations for intra- and intermolecular monomer structure factors on the accuracy of the coarse-graining procedure, as well as the relevance of higher-order corrections to their expression.