Strength Of Interaction Energy Research Articles

Kinetic network model to explain gain-of-function mutations in ERK2 enzyme.

ERK2 is a kinase protein that belongs to a Ras/Raf/MEK/ERK signaling pathway, which is activated in response to a range of extracellular signals. Malfunctioning of this cascade leads to a variety of serious diseases, including cancers. This is often caused by mutations in proteins belonging to the cascade, frequently leading to abnormally high activity of the cascade even in the absence of an external signal. One such "gain-of-function" mutation in the ERK2 protein, called a "sevenmaker" mutation (D319N), was discovered in 1994 in Drosophila. The mutation leads to disruption of interactions of other proteins with the D-site of ERK2 and results, contrary to expectations, in an increase of its activity in vivo. However, no molecular mechanism to explain this effect has been presented so far. The difficulty is that this mutation should equally negatively affect interactions of ERK2 with all substrates, activators, and deactivators. In this paper, we present a semiquantitative kinetic network model that gives a possible explanation of the increased activity of mutant ERK2 species. A simplified biochemical network for ERK2, viewed as a system of coupled Michaelis-Menten processes, is presented. Its dynamic properties are calculated explicitly using the method of first-passage processes. The effect of mutation is associated with changes in the strength of interaction energy between the enzyme and the substrates. It is found that the dependence of kinetic properties of the protein on the interaction energy is nonmonotonic, suggesting that some mutations might lead to more efficient catalytic properties, despite weakening intermolecular interactions. Our theoretical predictions agree with experimental observations for the sevenmaker mutation in ERK2. It is also argued that the effect of mutations might depend on the concentrations of substrates.

Inorganic benzenes as the noncovalent interaction donor: a study of the π-hole interactions.

For inorganic benzenes C3N3X3 and B3O3X3 (X=H, F, CN), the positive electrostatic potentials (π-hole) were discovered above and below the inorganic benzene ring center. Then, the π-hole interactions between the inorganic benzenes and NCH have been designed and investigated by MP2/aug-cc-pVDZ calculations. In this paper, the termolecular complexes B3O3X3···NCH···NCH, C3N3X3···NCH···NCH (X=H, F, CN) were also designed to illustrate the enhancing effects of the H···N hydrogen bond on the π-hole interactions. The π-hole interaction energy was influenced by the strength of different electron-withdrawing substituents of inorganic benzenes, gradually increasing in the order of X=H, F, CN. What's more, the π electron densities account for 71~88% of the total electron densities, indicating the strength of interaction energy is mainly determined by π-type electron densities. Graphical abstract The termolecular complexes B3O3X3···NCH···NCH, C3N3X3···NCH···NCH (X=H, F, CN) were designed to illustrate the enhancing effects of the H···N hydrogen bond on the π-hole interactions.

Optimal Definition of Inter-Residual Contact in Globular Proteins Based on Pairwise Interaction Energy Calculations, Its Robustness, and Applications

Although a contact is an essential measurement for the topology as well as strength of non-covalent interactions in biomolecules and their complexes, there is no general agreement in the definition of this feature. Most of the definitions work with simple geometric criteria which do not fully reflect the energy content or ability of the biomolecular building blocks to arrange their environment. We offer a reasonable solution to this problem by distinguishing between "productive" and "non-productive" contacts based on their interaction energy strength and properties. We have proposed a method which converts the protein topology into a contact map that represents interactions with statistically significant high interaction energies. We do not prove that these contacts are exclusively stabilizing, but they represent a gateway to thermodynamically important rather than geometry-based contacts. The process is based on protein fragmentation and calculation of interaction energies using the OPLS force field and relies on pairwise additivity of amino acid interactions. Our approach integrates the treatment of different types of interactions, avoiding the problems resulting from different contributions to the overall stability and the different effect of the environment. The first applications on a set of homologous proteins have shown the usefulness of this classification for a sound estimate of protein stability.

Molecular Dynamics Study of Extraordinary Elastic Deformation Found in Gold Atomic Cluster

Inelastic deformation of gold (Au) atomic cluster is investigated by using molecular dynamics (MD) simulations. We performed compression and unloading tests in which silicon (Si) plates approach each other and push single Au cluster of 4 nm diameter in between. Possibility of super-elastic (hyper-elastic) behavior is first discussed in the present study. The potential function of embedded atom method is adopted inside Au cluster, whereas other interactions are formulated by simplified Lennard-Jones interaction. The cluster in MD simulation shows large recovery strain which is reversible in unloading process after compression. The recovery strain is estimated on average from 5 to 10%. It is found that there are deformation mechanisms depending on temperature of the cluster. Mechanism for low temperature is based on slip motion and that for high temperature is dominated by surface reconstruction. The strength of interaction energy between Si plate and the Au cluster which may cause pulling force and produce tensile state is investigated, referring to our AFM experiment.

Pair dynamics in a glass-forming binary mixture: simulations and theory.

We have carried out molecular dynamics simulations to understand the dynamics of a tagged pair of atoms in a strongly nonideal glass-forming binary Lennard-Jones mixture. Here atom B is smaller than atom A (sigma(BB)=0.88sigma(AA), where sigma(AA) is the molecular diameter of the A particles) and the AB interaction is stronger than that given by Lorentz-Berthelot mixing rule (epsilon(AB)=1.5epsilon(AA), where epsilon(AA) is the interaction energy strength between the A particles). The generalized time-dependent pair distribution function is calculated separately for the three pairs (AA, BB, and AB). The three pairs are found to behave differently. The relative diffusion constants are found to vary in the order D(BB)(R)>D(AB)(R)>D(AA)(R), with D(BB)(R) approximately 2D(AA)(R), showing the importance of the hopping process (B hops much more than A). We introduce a non-Gaussian parameter [alpha(P)(2)(t)] to monitor the relative motion of a pair of atoms and evaluate it for all the three pairs with initial separations chosen to be at the first peak of the corresponding partial radial distribution functions. At intermediate times, significant deviation from the Gaussian behavior of the pair distribution functions is observed with different degrees for the three pairs. A simple mean-field (MF) model, proposed originally by Haan [Phys. Rev. A 20, 2516 (1979)] for one-component liquid, is applied to the case of a binary mixture and compared with the simulation results. While the MF model successfully describes the dynamics of the AA and AB pairs, the agreement for the BB pair is less satisfactory. This is attributed to the large scale anharmonic motions of the B particles in a weak effective potential. Dynamics of the next nearest neighbor pairs is also investigated.