Intrinsic Flexibility beyond the Highly Ordered DNA Tetrahedron: An Integrative Spectroscopic and Molecular Dynamics Approach.

Since the introduction of DNA-based architectures, in the past decade, DNA tetrahedrons have aroused great interest. Applications of such nanostructures require structural control, especially in the perspective of their possible functionalities. In this work, an integrated approach for structural characterization of a tetrahedron structure is proposed with a focus on the fundamental biophysical aspects driving the assembly process. To address such an issue, spin-labeled DNA sequences are chemically synthesized, self-assembled, and then analyzed by Continuous-Wave (CW) and pulsed Electron Paramagnetic Resonance (EPR) spectroscopy. Interspin distance measurements based on PELDOR/DEER techniques combined with molecular dynamics (MD) thus revealed unexpected dynamic heterogeneity and flexibility of the assembled structures. The observation of flexibility in these ordered 3D structures demonstrates the sensitivity of this approach and its effectiveness in accessing the main dynamic and structural features with unprecedented resolution.

General Approach to Coupled Reactive Smoluchowski Equations: Integration and Application of Discrete Variable Representation and Generalized Coordinate Methods to Diffusive Problems.

A new and more general approach to diffusion problems with the inclusion of reactivity among different coupled diffusional states is rationalized and presented. The integration of our previous developments in such a field [Phys. Chem. Chem. Phys., 2015, 17, 17362-17374; J. Chem. Theory Comput., 2016, 12, 3482-3490] are implemented in a software package tool allowing the generic user to set up and run diffusional calculations with very low efforts. We show the applicability of the whole framework to a generic diffusional case of chemical interest that is the study case of (N,N-dimethylamino)benzonitrile (DMABN) fluorescence, whose excited state undergoes twisted intramolecular charge transfer (TICT) relaxation. The population dynamics of the excited state coupled to the ground state is followed, and a fluorescence decay spectrum is calculated. The theoretical and numerical background here presented is robust and general enough to complement a wide number of diffusional problems of current interest.

Toward a General Yet Effective Computational Approach for Diffusive Problems: Variable Diffusion Tensor and DVR Solution of the Smoluchowski Equation along a General One-Dimensional Coordinate.

A generalization to arbitrary large amplitude motions of a recent approach to the evaluation of diffusion tensors [ J. Comput. Chem. , 2009 , 30 , 2 - 13 ] is presented and implemented in a widely available package for electronic structure computations. A fully black-box tool is obtained, which, starting from the generation of geometric structures along different kinds of paths, proceeds toward the evaluation of an effective diffusion tensor and to the solution of one-dimensional Smoluchowski equations by a robust numerical approach rooted in the discrete variable representation (DVR). Application to a number of case studies shows that the results issuing from our approach are identical to those delivered by previous software (in particular DiTe) for rigid scans along a dihedral angle, but can be improved by employing relaxed scans (i.e., constrained geometry optimizations) or even more general large amplitude paths. The theoretical and numerical background is robust and general enough to allow quite straightforward extensions in several directions (e.g., inclusion of reactive paths, solution of Fokker-Planck or stochastic Liouville equations, multidimensional problems, free-energy rather than electronic-energy driven processes).

Discrete variable representation of the Smoluchowski equation using a sinc basis set.

We present a new general framework for solving the monodimensional Smoluchowski equation using a discrete variable representation (DVR) based on the so called sinc basis set. The reliability of our implementation is assessed by comparing the convergence of diffusive operator eigenvalues calculated using our method and using a simple finite difference scheme for some model diffusive problems. The results here presented open encouraging possibilities for dealing with more complicated systems, where additional coordinate dependent terms in the equation or multidimensional treatments are needed and traditional methods often become unfeasible.

Probing the conformational energetics of alkyl thiols on gold surfaces by means of a morphing/steering non-equilibrium tool.

In this work we show that a non-equilibrium statistical tool based on Jarzynski's equality (JE) can be applied to achieve a sufficiently accurate mapping of the torsion free energy, bond-by-bond, for an alkyl thiol ligand tethered to a gold surface and sensing the presence of the surrounding cluster of similar chains. The strength of our approach is the employment of a strategy to let grow the internal energetics of the whole system (namely, the "energy morphing" stage recently presented by us in J. Comput. Chem., 2014, 35, 1865-1881) before initiating the rotational steering, which yields accurate results in terms of statistical uncertainties and bias on the free energy profiles. The work is mainly methodological and illustrates the feasibility of this kind of inspection on nanoscale molecular clusters with conformational flexibility. The outcomes for the archetype of self-assembled-monolayers considered here, a regular pattern of 10-carbon alkyl thiols on an ideal gold surface, give information on the conformational mobility of the ligands. Notably, such information is unlikely to be obtained by means of standard equilibrium techniques or by conventional molecular dynamics simulations.

Looking for some free energy? Call JEFREE ( ).

In this communication, we present the Jarzynski's Equality FREe Energy (JEFREE) library, an efficient and easy-to-use C++ library targeted to the calculation of the free energy profile along a selected generalized coordinate of a system, within the framework of the nonequilibrium steered transformations as introduced by Jarzynski [Phys. Rev. E, 1997, 56, 5018]. JEFREE can be readily integrated into any code, since both C and FORTRAN wrappers have been developed, and easily customizable by a user thanks to the object-oriented programming paradigm offered by the C++ language. Also, JEFREE implements the novel idea of making a total "morphing" of the system energy landscape before initiating the proper steering stage. This proves to be an efficient mean to overtake the problematic sampling of the initial equilibrium state when the number of degrees of freedom is high and the landscape owns many local minima separated by large energy barriers. The calculation of the free energy profile for the rotation along torsion angles in alkyl chains is presented as an example of application of our tool.