Density-functional-theory approach to the Hamiltonian adaptive resolution simulation method.

In the Hamiltonian adaptive resolution simulation method (H-AdResS) it is possible to simulate coexisting atomistic (AT) and ideal gas representations of a physical system that belong to different subdomains within the simulation box. The Hamiltonian includes a field that bridges both models by smoothly switching on (off) the intermolecular potential as particles enter (leave) the AT region. In practice, external one-body forces are calculated and applied to enforce a reference density throughout the simulation box, and the resulting external potential adds up to the Hamiltonian. This procedure suggests an apparent dependence of the final Hamiltonian on the system's thermodynamic state that challenges the method's statistical mechanics consistency. In this paper, we explicitly include an external potential that depends on the switching function. Hence, we build a grand canonical potential for this inhomogeneous system to find the equivalence between H-AdResS and density functional theory (DFT). We thus verify that the external potential inducing a constant density profile is equal to the system's excess chemical potential. Given DFT's one-to-one correspondence between external potential and equilibrium density, we find that a Hamiltonian description of the system is compatible with the numerical implementation based on enforcing the reference density across the simulation box. In the second part of the manuscript, we focus on assessing our approach's convergence and computing efficiency concerning various model parameters, including sample size and solute concentrations. To this aim, we compute the excess chemical potential of water, aqueous urea solutions and Lennard-Jones (LJ) mixtures. The results' convergence and accuracy are convincing in all cases, thus emphasising the method's robustness and capabilities.

Communication: Kirkwood-Buff integrals in the thermodynamic limit from small-sized molecular dynamics simulations.

We present an accurate and efficient method to obtain Kirkwood-Buff (KB) integrals in the thermodynamic limit from small-sized molecular dynamics simulations. By introducing finite size effects into integral equations of statistical mechanics, we derive an analytical expression connecting the KB integrals of the bulk system with the fluctuations of the number of molecules in the corresponding closed system. We validate the method by calculating the activity coefficients of aqueous urea mixtures and the KB integrals of Lennard-Jones fluids. Moreover, our results demonstrate how to identify simulation conditions under which computer simulations reach the thermodynamic limit.

Statistical mechanics of Hamiltonian adaptive resolution simulations.

The Adaptive Resolution Scheme (AdResS) is a hybrid scheme that allows to treat a molecular system with different levels of resolution depending on the location of the molecules. The construction of a Hamiltonian based on the this idea (H-AdResS) allows one to formulate the usual tools of ensembles and statistical mechanics. We present a number of exact and approximate results that provide a statistical mechanics foundation for this simulation method. We also present simulation results that illustrate the theory.

Quantum locality and equilibrium properties in low-temperature parahydrogen: a multiscale simulation study.

Parahydrogen is the spin-zero singlet state of molecular hydrogen, which at low temperature (between 14 and 25 K) is in a fluid state. A classical treatment of the system leads to unphysical freezing, and the inclusion of quantum delocalization of the molecule is then required to obtain a realistic description of its equilibrium properties. In the present work, we employ the classical-quantum adaptive resolution method AdResS to investigate the spatial extension of quantum delocalization effects in the bulk fluid at low temperature. Specifically, we simulate a small, spherical region of the system in full quantum detail: this region is coupled to a bulk of coarse-grained particles with classical, quantum-derived effective interactions obtained from quantum simulations. The two regions are interfaced through open boundaries and in conditions of thermodynamic equilibrium. Structural properties of the fluid, namely, pair distribution functions, are measured for different sizes of the quantum region. The results of this work show that, for the thermodynamic conditions corresponding to the range of temperature between 14 and 25 K, the bead-based, quantum structural properties of low-temperature parahydrogen are deemed local and do not require the support of an explicit quantum bulk.

ALADYN: a web server for aligning proteins by matching their large-scale motion.

The ALADYN web server aligns pairs of protein structures by comparing their internal dynamics and detecting regions that sustain similar large-scale movements. The latter often accompany functional conformational changes in proteins and enzymes. The ALADYN dynamics-based alignment can therefore highlight functionally-oriented correspondences that could be more elusive to sequence- or structure-based comparisons. The ALADYN server takes the structure files of the two proteins as input. The optimal relative positioning of the molecules is found by maximizing the similarity of the pattern of structural fluctuations which are calculated via an elastic network model. The resulting alignment is presented via an interactive graphical Java applet and is accompanied by a number of quantitative indicators and downloadable data files. The ALADYN web server is freely accessible at the http://aladyn.escience-lab.org address.

PiSQRD: a web server for decomposing proteins into quasi-rigid dynamical domains.

SUMMARY: The PiSQRD web resource can be used to subdivide protein structures in quasi-rigid dynamical domains. The latter are groups of amino acids behaving as approximately rigid units in the course of protein equilibrium fluctuations. The PiSQRD server takes as input a biomolecular structure and the desired fraction of protein internal fluctuations that must be accounted for by the relative rigid-body motion of the dynamical domains. Next, the lowest energy modes of fluctuation of the protein (optionally provided by the user) are calculated and used to identify the rigid subunits. The resulting optimal subdivision is returned through a web page containing both interactive graphics and detailed data output. AVAILABILITY: The PiSQRD web server, which requires Java, is available free of charge for academic users at http://pisqrd.escience-lab.org.

Coarse-grained description of protein internal dynamics: an optimal strategy for decomposing proteins in rigid subunits.

The possibility of accurately describing the internal dynamics of proteins, in terms of movements of a few approximately-rigid subparts, is an appealing biophysical problem with important implications for the analysis and interpretation of data from experiments or numerical simulations. The problem is tackled here by means of a novel variational approach that exploits information about equilibrium fluctuations of interresidues distances, provided, e.g., by atomistic molecular dynamics simulations or coarse-grained models. No contiguity in primary sequence or in space is enforced a priori for amino acids grouped in the same rigid unit. The identification of the rigid protein moduli, or dynamical domains, provides valuable insight into functionally oriented aspects of protein internal dynamics. To illustrate this point, we first discuss the decomposition of adenylate kinase and HIV-1 protease and then extend the investigation to several representatives of the hydrolase enzymatic class. The known catalytic site of these enzymes is found to be preferentially located close to the boundary separating the two primary dynamical subdomains.