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Protein-protein interaction plays an important role in the development of almost all cells. Elucidating the dynamic binding and affinity of a protein-protein complex is essential for understanding the biological functions of proteins. EphA6 and Odin proteins are members of the Eph (erythropoietin-producing hepatocyte) receptor family and the Anks (ankyrin repeat and sterile α motif domain-containing) family, respectively. Odin significantly functions in regulating endocytosis, degradation, and stability of EphA receptors. In this work, the key residues of the interaction interface were determined through a hydrogen bond, root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and dynamic correlation analysis of the conventional molecular dynamics (MD) simulations. The calculated standard binding free energy, -7.92 kcal/mol, between EphA6 and Odin is quite consistent with the experimental measurement value, -8.73 kcal/mol. By the combination of several MD simulation techniques, our investigation of the binding process reveals the detailed representative characteristics of the entire binding pathway at the molecular level. Based on the obtained potential of the mean force (PMF) curve, the analysis of the simulation trajectories shows that the residue Arg1013 in the receptor EphA6 is responsible for capturing Asp739 and Asp740 in the ligand Odin during the initial stage of binding. In the later stage of binding, the hydrogen bonds and salt bridges between a series of residues Lys973, Leu1007, Gly1009, His1010, and Arg1012 in the receptor and residues Leu735, Asn736, Asp739, Asp740, and Asp753 in the ligand mainly contribute to the stability of the protein complex. In addition, the specific change process of the receptor-ligand-binding mode is also clarified during the binding process. Our present simulation will promote a deep understanding of the protein-protein interaction, and the identified key interresidue interaction will be theoretical guidance for the design of protein drugs.

Electrospray ionization can generate microsolvated multiply charged metal ions for various metals and ligands, allowing exploration of chemistry within such clusters. The finite size of these systems permits comparing experimental results with accurate calculations, creating a natural laboratory to research ion solvation. Mass spectrometry has provided much insight into the stability and dissociation of ligated metal cations. While solvated singly charged ions tend to shrink by ligand evaporation, solvated polycations below a certain size exhibit charge reduction and/or ligand fragmentation due to organometallic reactions. Here we investigate the acetone complexes of representative divalent metals (Ca, Mn, Co, Ni, and Cu), comparing the results of collision-induced dissociation with the predictions of density functional theory. As for other solvated dications, channels involving proton or electron transfer compete with ligand loss and become dominant for smaller complexes. The heterolytic C-C bond cleavage is common, like in DMSO and acetonitrile complexes. Of primary interest is the unanticipated neutral ethylene loss, found for all metals studied except Cu and particularly intense for Ca and Mn. We focus on understanding that process in the context of competing dissociation pathways, as a function of metal identity and number of ligands. According to first-principles modeling, ethylene elimination proceeds along a complex path involving two intermediates. These results suggest that chemistry in microsolvated multiply charged ions may still hold major surprises.

The structural properties of the cluster series Me(m)Si(7-m) (Me = Cu and Li, m < or = 6) are studied by density functional theory (DFT) employing a plane wave basis. The equilibrium geometries and energetic properties of these clusters are obtained by use of the simulated annealing procedure in conjunction with the Nosé thermostat algorithm. The lowest energy isomer thus obtained is analyzed by density functional theory at the B3LYP/6-311+G(d,p) level including all electrons. Pentagonal ground state structures derived from the D(5)(h) equilibrium geometries of both Si(7) and Cu(7) are obtained for Cu(m)Si(7-m) with m < 6. The Li(m)Si(7-m) clusters, in contrast, tend toward adsorption geometries where m Li atoms are attached to a Si(7-m)framework with pronounced negative charge. For both Li(m)Si(7-m) and Cu(m)Si(7-m), a marked decrease of the energy gap is found as the number of metal atom constituents increases.