I wish for you, with your newfound, immense skill in protein structure analysis, to consider α/β proteins. We shall consider TIM barrels, Rossmann folds, TOPRIM domains, ATPases, and kinases. Many more examples are available than we shall cover.

α/β Proteins

We derive the coarse-grained interactions between DNA nucleotides from ab initio total-energy calculations based on density functional theory (DFT). The interactions take into account base and sequence specificity, and are decomposed into physically distinct contributions that include hydrogen bonding, stacking interactions, backbone, and backbone-base interactions. The interaction energies of each contribution are calculated from DFT for a wide range of configurations and are fitted by simple analytical expressions for use in the coarse-grained model, which reduces each nucleotide into two sites. This model is not derived from experimental data, yet it successfully reproduces the stable B-DNA structure and gives good predictions for the persistence length. It may be used to realistically probe dynamics of DNA strands in various environments at the μs time scale and the μm length scale.

Ab initio determination of coarse-grained interactions in double stranded DNA

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.

/pdf/bottom-up-coarse-grained-modeling-of-dna-2fvn84x8kb.pdf

Bottom-Up Coarse-Grained Modeling of DNA.

Transitions between the B and A forms of a short DNA double helix (12 base pairs) at different salt concentrations in an aqueous solution have been studied by the molecular dynamics method in the framework of a coarse-grained model with explicit ions but without friction. It has been shown that the A-DNA, stable at high salt concentrations, is a dynamic conglomerate of the molecule and the ions coming from the solution into the deep major groove and then leaving it. In such a short helix, in the model without friction, even at low salt concentrations, transitions from B-DNA to A-DNA and back are frequent and fast. Stable ADNA (without transitions to B-DNA) forms at salt concentrations greater than 0.45 mol/L.

MD simulation of the transitions between B-DNA and A-DNA in the framework of a coarse-grained model

In the framework of the ‘sugar’ coarse-grained DNA model [N.A. Kovaleva, I.P. Koroleva (Kikot), M.A. Mazo, Journal of Molecular Modeling 23(2):66 (2017), https://doi.org/10.1007/s00894-017-3209-z], we study the transition between B and A forms of a short DNA molecule (12 base pairs) when the concentration of salt changes. The model exploits the explicit ions and implicit water representation and allows to separately change the friction of the ions and of the DNA molecule. We compare the behavior of the system for different values of friction which proved to not affect the order of the transition, but allowed to determine the roles of the DNA and the ions in the behavior of the conglomerate. We find the order (the first) and the point of the transition (0.316 M) in the case of ‘inviscid’ water (zero friction for both the ions and the DNA, the NVE ensemble). The helix consisting of 12 bp (more than thousand atoms) proved to exhibit the features of small systems. Namely, even at low salt concentrations, one can observe the jumps from B-DNA to A-DNA and back. We analyse the structure of the A-DNA and find the reasons for such a behavior.

B\(\leftrightarrow \)A Transition in a Short DNA Molecule

More than 20 coarse-grained (CG) DNA models have been developed for simulating the behavior of this molecule under various conditions, including those required for nanotechnology. However, none of these models reproduces the DNA polymorphism associated with conformational changes in the ribose rings of the DNA backbone. These changes make an essential contribution to the DNA local deformability and provide the possibility of the transition of the DNA double helix from the B-form to the A-form during interactions with biological molecules. We propose a CG representation of the ribose conformational flexibility. We substantiate the choice of the CG sites (six per nucleotide) needed for the "sugar" GC DNA model, and obtain the potentials of the CG interactions between the sites by the "bottom-up" approach using the all-atom AMBER force field. We show that the representation of the ribose flexibility requires one non-harmonic and one three-particle potential, the forms of both the potentials being different from the ones generally used. The model also includes (i) explicit representation of ions (in an implicit solvent) and (ii) sequence dependence. With these features, the sugar CG DNA model reproduces (with the same parameters) both the B- and A- stable forms under corresponding conditions and demonstrates both the A to B and the B to A phase transitions. Graphical Abstract The proposed coarse-grained DNA model allows to reproduce both the B- and A- DNA forms and the transitions between them under corresponding conditions.

I P Koroleva Kikot

Papers

The “sugar” coarse-grained DNA model