Sampling and convergence in free energy calculations of protein-ligand interactions: The binding of triphenoxypyridine derivatives to factor Xa and trypsin

The binding of a set of 10 triphenoxypyridine derivatives to two serine proteases, factor Xa and trypsin, has been used to analyze factors related to sampling and convergence in free energy calculations based on molecular dynamics simulation techniques. The inhibitors investigated were initially proposed as part of the Critical Assessment of Techniques for Free Energy Evaluation (CATFEE) project for which no experimental results nor any assessment of the predictions submitted by various groups have ever been published. The inhibitors studied represent a severe challenge for explicit free energy calculations. The mutations from one compound to another involve up to 19 atoms, the creation and annihilation of net charge and several alternate binding modes. Nevertheless, we demonstrate that it is possible to obtain highly converged results (+/- 5-10 kJ/mol) even for such complex multi-atom mutations by simulating on a nanosecond time scale. This is achieved by using soft-core potentials to facilitate the creation and deletion of atoms and by a careful choice of mutation pathway. The results show that given modest computational resources, explicit free energy calculations can be successfully applied to realistic problems in drug design.     

Prediction of some nuclear properties of actinides

The 2Z–N correlations are indications for the deuteron-triton (d-t) cluster structure of most of the nuclei. For N=Z nuclei this approach indicates deuteron (d) clusters only. The space-dependent Schrödinger equation for neutron and proton in the same shell for N=Z nuclei shows that part of the time these particles behave like single particles and part of the time as a deuteron clusters. The 2N–N correlations are used to predict some nuclear properties of many actinides.     

Cargo ships routing and scheduling: Survey of models and problems

When a ship costs thousands of dollars per day, significant savings can be achieved by proper fleet routing and scheduling. In contrast to vehicle scheduling, relatively little work has been done in ship routing and scheduling. This paper discusses briefly the differences between vehicle and ship routing and scheduling and the reasons for the low attention to ship scheduling in the past. The various modes of operation of cargo ships are described and a classification scheme for ship routing and scheduling models and problems is proposed. A review of ship routing, scheduling and related models is provided. The review is broken down into the following categories: transportation system models, liner operations, tramp shipping, industrial operations and other models. Finally, recent trends in ship scheduling, shortcomings in existing models and requirements from realistic models are discussed.     

Cooperative dynamics in two dimensions

We report results from molecular dynamics simulations of cooperative motion in a quasi-two-dimensional system of colloid particles. We find that the onset of the deviation of the single-particle displacement distribution from Gaussian form starts in the liquid phase and extends, with increasing magnitude, through the hexatic phase into the crystalline phase. The time for which the deviation is maximum increases exponentially with the density. As the density increases toward the hexatic phase a third dynamical relaxation mode emerges. We argue that the collective motion is generated by superpositions of instantaneous normal mode vibrations, with lifetimes that increase with the density, along paths with strong bond-orientation correlation.     

In vivo mapping of functional domains and axonal connectivity in cat visual cortex using magnetic resonance imaging

Noninvasive cognitive neuroimaging studies based on functional magnetic resonance imaging (fMRI) are of ever-increasing importance for basic and clinical neurosciences. The explanatory power of fMRI could be greatly expanded, however, if the pattern of the neuronal circuitry underlying functional activation could be made visible in an equally noninvasive manner. In this study, blood oxygenation level-dependent (BOLD)-based fMRI and diffusion tensor imaging (DTI) were performed in the same cat visual cortex, and the foci of fMRI activation utilized as seeding points for 3D DTI fiber reconstruction algorithms, thus providing the map of the axonal circuitry underlying visual information processing. The methods developed in this study will lay the foundation for in vivo neuroanatomy and the ability for noninvasive longitudinal studies of brain development.     

Can the eigenstates of a many-body Hamiltonian be represented exactly using a general two-body cluster expansion?

It is proved that a recent conjecture that the exact ground-state wave function of an arbitrary many-fermion system with one- and two-body interactions may be represented by an exponential cluster expansion employing finite two-body operators, starting from any reference function sufficiently close to the exact eigenfunction, is not valid. We show that the space of initial reference functions which lead to the exact ground state is of dimension equal to the number of two-body operators. If the dimension of the multiparticle space is greater than the number of two-body operators, then the space of good reference functions is of measure zero in it.