No abstract

We present software package MagiC, which is designed to perform systematic structure-based coarse graining of molecular models. The effective pairwise potentials between coarse-grained sites of low-resolution molecular models are constructed to reproduce structural distribution functions obtained from the modeling of the system in a high resolution (atomistic) description. The software supports coarse-grained tabulated intramolecular bond and angle interactions, as well as tabulated nonbonded interactions between different site types in the coarse-grained system, with the treatment of long-range electrostatic forces by the Ewald summation. Two methods of effective potential refinement are implemented: iterative Boltzmann inversion and inverse Monte Carlo, the latter accounting for cross-correlations between pair interactions. MagiC uses its own Metropolis Monte Carlo sampling engine, allowing parallel simulation of many copies of the system with subsequent averaging of the properties, which provides fast convergence of the method with nearly linear scaling at parallel execution.

Accurate parametrization of force fields (FFs) is of ultimate importance for computer simulations to be reliable and to possess a predictive power. In this work, we analyzed, in multi-microsecond simulations of a 40-base-pair DNA fragment, the performance of four force fields, namely, the two recent major updates of CHARMM and two from the AMBER family. We focused on a description of double-helix DNA flexibility and dynamics both at atomistic and at mesoscale level in coarse-grained (CG) simulations. In addition to the traditional analysis of different base-pair and base-step parameters, we extended our analysis to investigate the ability of the force field to parametrize a CG DNA model by structure-based bottom-up coarse-graining, computing DNA persistence length as a function of ionic strength. Our simulations unambiguously showed that the CHARMM36 force field is unable to preserve DNA’s structural stability at over-microsecond time scale. Both versions of the AMBER FF, parmbsc0 and parmbsc1, showed good agreement with experiment, with some bias of parmbsc0 parameters for intermediate A/B form DNA structures. The CHARMM27 force field provides stable atomistic trajectories and overall (among the considered force fields) the best fit to experimentally determined DNA flexibility parameters both at atomistic and at mesoscale level.

The effective solvent-mediated potentials for Na + and Cl À ions in aqueous solution were calculated in a wide range of temperatures from 0 to 100 1C. The potentials have been determined using the inverse Monte Carlo approach, from the ion-ion radial distribution functions computed in 50 ns molecular dynamics simulations of ions and explicit water molecules. We further separated the effective potentials into a short-range part and an electrostatic long-range part represented by a coulombic potential with some dielectric permittivity. We adjusted the value of the dielectric permittivity to provide the fastest possible decay of the short-range potentials at larger distances. The obtained temperature dependence of the dielectric permittivity follows well the experimental data. We show also that the largest part of the temperature dependence of the effective potentials can be attributed to the temperature-dependent dielectric permittivity.

No abstract

Recent advances in methodology enable effective coarse-grained modeling of deoxyribonucleic acid (DNA) based on underlying atomistic force field simulations. The so-called bottom-up coarse-graining practice separates fast and slow dynamic processes in molecular systems by averaging out fast degrees of freedom represented by the underlying fine-grained model. The resulting effective potential of interaction includes the contribution from fast degrees of freedom effectively in the form of potential of mean force. The pair-wise additive potential is usually adopted to construct the coarse-grained Hamiltonian for its efficiency in a computer simulation. In this review, we present a few well-developed bottom-up coarse-graining methods, discussing their application in modeling DNA properties such as DNA flexibility (persistence length), conformation, “melting,” and DNA condensation.

DNA condensation and phase separation is of utmost importance for DNA packing in vivo with important applications in medicine, biotechnology and polymer physics. The presence of hexagonally ordered DNA is observed in virus capsids, sperm heads and in dinoflagellates. Rigorous modelling of this process in all-atom MD simulations is presently difficult to achieve due to size and time scale limitations. We used a hierarchical approach for systematic multiscale coarse-grained (CG) simulations of DNA phase separation induced by the three-valent cobalt(III)-hexammine (CoHex 3+ ). Solvent-mediated effective potentials for a CG model of DNA were extracted from all-atom MD simulations. Simulations of several hundred 100-bp-long CG DNA oligonucleotides in the presence of explicit CoHex 3+ ions demonstrated aggregation to a liquid crystalline hexagonally ordered phase. Following further coarse-graining and extraction of effective potentials, we conducted modelling at mesoscale level. In agreement with electron microscopy observations, simulations of an 10.2-kb-long DNA molecule showed phase separation to either a toroid or a fibre with distinct hexagonal DNA packing. The mechanism of toroid formation is analysed in detail. The approach used here is based only on the underlying all-atom force field and uses no adjustable parameters and may be generalised to modelling chromatin up to chromosome size.

We present a framework for coarse-grained modelling of the interface between foreign nanoparticles (NP) and biological fluids and membranes. Our model includes united-atom presentations of membrane lipids and globular proteins in implicit solvent, which are based on all-atom structures of the corresponding molecules and parameterised using experimental data or atomistic simulation results. The NPs are modelled by homogeneous spheres that interact with the beads of biomolecules via a central force that depends on the NP size. The proposed methodology is used to predict the adsorption energies for human blood plasma proteins on NPs of different sizes as well as the preferred orientation of the molecules upon adsorption. Our approach allows one to rank the proteins by their binding affinity to the NP, which can be used for predicting the composition of the NP-protein corona for the corresponding material. We also show how the model can be used for studying NP interaction with a lipid bilayer membrane and thus can provide a mechanistic insight for modelling NP toxicity.