A charge equilibration formalism for treating charge transfer effects in MD simulations: Application to water clusters.

Conventional classical force fields by construction do not explicitly partition intermolecular interactions to include polarization and charge transfer effects, whereas fully quantum mechanical treatments allow a means to effect this dissection (although not uniquely due to the lack of a charge transfer operator). Considering the importance of polarization in a variety of systems, a particular class of classical models, charge equilibration models, have been extensively developed to study those systems; since these types of interaction models are inherently based on movement of charge throughout a system, they are natural platform for including polarization and charge transfer effects within the context of molecular simulations. Here, we present two bond-space charge equilibration models we term as QE2 and mixed QE2 treat charge transfer in classical molecular mechanical calculations those provide practical solutions to two major drawbacks of charge equilibration models: (a) a nonvanishing amount of charge transfer between two heteroatoms at large separations, and (b) superlinear polarizability scaling during bond dissociation due to charge transfer over unphysical, large distances. To control charge transfer during dissociation of a bond in a molecular system, we introduce a distance-dependent scaling function (QE2 model) which, controls and recovers physical behavior of the homonuclear and heteronuclear charge transfer between two atoms at small and large values of internuclear separation; and the mixed QE2 model in which we combine the QE2 model under allow and disallow charge transfer situations that describe both charge transfer and polarizability in a distance-dependent manner. We demonstrate the utility of both models in the case of a water dimer, and compare the results with other existing models, and further, we perform short molecular dynamics simulations for few water clusters with the QE2 model to show the charge transfer and internuclear separation are correlated in dynamics. © 2017 Wiley Periodicals, Inc.

Anticipating response function in gene regulatory networks.

The origin of an ordered genetic response of a complex and noisy biological cell is intimately related to the detailed mechanism of protein-DNA interactions present in a wide variety of gene regulatory (GR) systems. However, the quantitative prediction of genetic response and the correlation between the mechanism and the response curve is poorly understood. Here, we report in silico binding studies of GR systems to show that the transcription factor (TF) binds to multiple DNA sites with high cooperativity spreads from specific binding sites into adjacent non-specific DNA and bends the DNA. Our analysis is not limited only to the isolated model system but also can be applied to a system containing multiple interacting genes. The controlling role of TF oligomerization, TF-ligand interactions, and DNA looping for gene expression has been also characterized. The predictions are validated against detailed grand canonical Monte Carlo simulations and published data for the lac operon system. Overall, our study reveals that the expression of target genes can be quantitatively controlled by modulating TF-ligand interactions and the bending energy of DNA.