Monte Carlo simulations nucleic acids

R. Rohs, 1. Bloch, H. Sklenar, and Z. Shakked, Molecular flexibility in ab initio drug docking to DNA binding-site and binding-mode transitions in all-atom Monte Carlo simulations, Nucleic Acids Research, vol. 33, no. 22, pp. 7048-7057, 2005. 

Sklenar, H., Wiistner, D., Rohs, R. Using internal and collective variables in Monte Carlo simulations of nucleic acid structures chain breakage/closure algorithm and associated Jacobians. J. Comput. Chem. 2006, 27, 309-15. 

Soon the excitement to see for the first time graphical representations of computed solvation shells for solvated ions from Monte Carlo simulations [81]. The next step was to go to even more complex systems, like enzymes, proteins, and particularly nucleic acids, A-DNA [82], B-DNA [83], without and with counterions [84] and in solution. The quantum biology community was taken by surprise, but soon accepted the new path as a new but necessary computational standard. I was proud to have forcefully recalled that the correct dictionary of quantum biology must contain terms like temperature, volume and free energy eventually, I was elected president of the International Society of Quantum Biology. 

Fig. 11. Nucleic acids B-DNA domain operation modes Backbone flexibilities mediating A-B transitions and intercalation geometries - an instrumentation assumed to be partially based on nonlinear excitations.31 Modified from refs. 32 and 33 (top). Water molecules connectivity pathways and Na+ counterion orientations from low to high humidity as resulting from extended Monte Carlo simulations. Modified from t ef. 34 (bottom).

The application of Monte Carlo method for the study of hydration of nucleic acids, their components [77-80], and hydration of the DNA-ligand complexes (for example, dCpG with proflavine [81] and DNA with azinomycin B [82] intercalated complexes) was described in literature in detail. Monte Carlo simulations enable to evaluate the low energy conformations of various complexes of DNA fragments. 

Shestopalova AV (2002) Hydration of nucleic acids components in dependence of nucleotide eomposition and relative humidity a Monte Carlo simulation. Europ Phys J D 20(l) 331-337... 

Intermolecular Interactions by Perturbation Theory Molecular Dynamics and Hybrid Monte Carlo in Systems with Multiple Time Scales and Long-range Forces Reference System Propagator Algorithms Molecular Dynamics Simulations of Nucleic Acids Molecular Dynamics Studies of Lipid Bilayers Molecular Dynamics Techniques and Applications to Proteins Monte Carlo Simulations for Liquid Monte Carlo Simulations for Polymers. 

There are basically two ways to overcome such problems. Firstly, one can thermally excite the system so that it can escape from local minima and continue to search the surrounding conformational space. This is the principle behind molecular dynamics simulations, which generate the trajectory of a molecule in time by numerically integrating Newton s equations of motion. This technique is discussed in another section of the present volume. It is also the principle behind Monte Carlo simulations, which build up a thermodynamic ensemble of molecular conformations based on their Boltzmann probabilities. Application of this approach to nucleic acids is discussed below. 

The Jumna program operates in internal coordinates and helicoidal parameters. It can be used for the minimization and Monte Carlo simulations on large nucleic acid sequences. It also allows one to study nucleic acid interactions with ligands and to design modified oligonucleotides aimed at specific target DNA. 

OPTS (Optim i/.ed Potentials for Liquid Simulations) is based on a force field developed by the research group of Bill Jorgensen now at Yale University and previously at Purdue University. Like AMBER, the OPLS force field is designed for calculations on proteins an d nucleic acids. It in troduces non bonded in leraclion parameters that have been carefully developed from extensive Monte Carlo liquid sim u lation s of small molecules. These n on-bonded interactions have been added to the bonding interactions of AMBER to produce a new force field that is expected to be better than AMBER at describing simulations w here the solvent isexplic-... 

A number of methodologies have been developed and generalized in recent years to quantitatively describe the ion atmosphere around nucleic acids [11, 12, 17, 28, 29]. These include models based on Poisson-Boltzmann equation [11, 12], counterion condensation [17], and simulation methods, such as Monte Carlo, molecular dynamics, and Brownian dynamics [28, 29]. 

Beveridge DL, Maye PV, Jayaram B, Ravishanker G, Mezei M (1984) Aqueous hydration of nucleic acid constituents Monte Carlo computer simulation studies. J Biomol Struct Dynam 2 261-270... 

Danilov VI, Zheltovsky NV, Slyusarchuk ON, Poltev VI, Alderfer JL (1997) The study of the stability of Watson-Crick nucleic acid base pairs in water and dimethyl sulfoxide eom-puter simulation by the Monte Carlo method. J Biomol Struct Dyn 15(l) 69-80... 

---