RESUMO
We introduced a conformational sampling method in an earlier report: The multi-dimensional virtual-system coupled molecular dynamics (mD-VcMD) enhances conformational sampling of a biomolecular system by computer simulations. Herein, new sampling method, a subzone-based mD-VcMD, is presented as an extension of mD-VcMD. Then, the subzone-based method is extended further using a genetic algorithm (GA) named the GA-guided mD-VcMD. In these methods, iterative simulation runs are performed to increase the sampled region gradually. The new methods have the following benefits: (1) They are free from a production run: i.e., all snapshots from all iterations are useful for analyses. (2) They are free from fine tuning of a weight function (probability distribution function or potential of mean force). (3) A canonical ensemble (i.e., a thermally equilibrated ensemble) is generated from a simple procedure. A thermodynamic weight is assigned to each snapshot. (4) Selective sampling can be performed for particularly addressing a poorly sampled region without breaking the proportion of the canonical ensemble if the poorly sampled conformational region emerges in sampling. By applying the methods to a simple system that involves an energy barrier between potential-energy minima, we demonstrated that the new methods have considerably higher sampling efficiency than the original mD-VcMD does.
RESUMO
Medical societies, which boast the elite of the medical circles, have not only important historic missions but also great advantages in public health advancement. For this reason, their role in the following aspects ought to be brought into greater play: stepping up research on the situation and trends of public health advancement; intensifying perspective study on the prevention and treatment abroad of infectious diseases; reinforcing health education for all people; carrying out continuing medical education with regard to seasonal infectious diseases; offering prevention and treatment guidance in public health via long distance consultation networks; and making concerted efforts in tackling key problems by making use of quality human resources.
