The evaluation of reduction potentials of proteins by ab initio approaches presents a major challenge for computational chemistry. This is addressed in the present investigation by reporting detailed calculations of the reduction potentials of the blue copper proteins plastocyanin and rusticyanin using the QM/MM all-atom frozen density functional theory, FDFT, method. The relevant ab initio free energies are evaluated by using a classical reference potential. This approach appears to provide a general consistent and effective way for reproducing the configurational ensemble needed for consistent ab initio free energy calculations. The FDFT formulation allows us to treat a large part of the protein quantum mechanically by a consistently coupled QM/QM/MM embedding method while still retaining a proper configurational sampling. To establish the importance of proper configurational sampling and the need for a complete representation of the protein+solvent environment, we also consider several classical approaches. These include the semi-macroscopic PDLD/S-LRA method and classical all-atom simulations with and without a polarizable force field. The difference between the reduction potentials of the two blue copper proteins is reproduced in a reasonable way, and its origin is deduced from the different calculations. It is found that the protein permanent dipole tunes down the reduction potential for plastocyanin compared to the active site in regular water solvent, whereas in rusticyanin it is instead tuned up. This electrostatic environment, which is the major effect determining the reduction potential, is a property of the entire protein and solvent system and cannot be ascribed to any particular single interaction.

The empirical valence bond (EVB) model provides an extremely powerful way for modeling and analyzing chemical reactions in solutions and proteins. However, this model is based on the unverified assumption that the off diagonal elements of the EVB Hamiltonian do not change significantly upon transfer of the reacting system from one phase to another. This ad hoc assumption has been rationalized by its consistency with empirically observed linear free energy relationships, as well as by other qualitative considerations. Nevertheless, this assumption has not been rigorously established. The present work explores the validity of the above EVB key assumption by a rigorous numerical approach. This is done by exploiting the ability of the frozen density functional theory (FDFT) and the constrained density functional theory (CDFT) models to generate convenient diabatic states for QM/MM treatments, and thus to examine the relationship between the diabatic and adiabatic surfaces, as well as the corresponding effective off diagonal elements. It is found that, at least for the test case of S(N)()2 reactions, the off diagonal element does not change significantly upon moving from the gas phase to solutions and thus the EVB assumption is valid and extremely useful.

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Biological surfaces are very complex in nature. They have wide distribution in molecular species; including positive and negative charges, polar and non-polar groups. [1] A material to show adhesion to such biological surfaces should have the capability of creating enough adhesive interacting sites with these species in wet environment. [2] Conventional hydrogels usually have poor adhesion to biological surfaces. [3] This is because the adhesion in wet environment is usually based on the Columbic interaction that strongly depends on the charge combinations. [3,4] Many of the biological surfaces and hydrogels have net negative surface charge [5] and they are repulsive in water. Developing adhesives that possess the ability of quick, strong, and reversible adhesion to hydrogels and biological tissues regardless their net charge identity will substantially promote the application of hydrogels in biomedical applications. Several research groups have tried to develop different adhesive hydrogels based on surface modification, [6] mechanical interlocking, [7] making composites, [8] supramolecular recognition, [9] and nano-particles. [10,11] But these approaches have limitations in practical applications, such as lengthy and complicated way of processing, lack of water resistivity and universality, inability in non-residual removal, etc. [12] The clue to develop adhesives working for hydrogels and biological tissues hides in nature.Bacteria cells, ubiquitous in environment, can attach with almost any surfaces including human tissues, regardless the diversity in the surface chemistry. The self-adjustable capability of the extracellular polymeric matrix (EPM) of bacteria cells has made this possible. [13,14] EPM can provide sufficient interacting sites for adsorption of species at interface in response to substrates mechanical and chemical properties through re-distribution of their charged groups. [15] Inspired from nature, we intend to find out a self-adjustable hydrogel adhesive for adhesion to hydrogels and tissues. A self-adjustable surface is such a surface which can offer its species for the formation of attractive interaction depending on substrate charges through dynamic reorganization process. A possible design for achieving such a self-adjustable 3 adhesive is a hydrogel composed of both positively and negatively charged monomers.Presence of both charges in the hydrogel is expected to create attractive interacting sites with any charged surfaces regardless of their charge identity to facilitate adsorption. But this seems to be tricky, because incorporation of both type charges in the same hydrogel sometime encounters strong self-ionic association, which will made it impossible for the formation of bonds with other species residing in different surfaces or in some cases imbalance in component inside hydrogel offers a strong net charge over the surface, [16] which will prevent their non-specific adhesion property. We can overcome this problem by choosing a neutral (charge balanced) polyampholyte (PA) hydrogel th...

Recently, we have reported that polyampholytes, synthesized from free radical copolymerization of anionic monomer and cationic monomer, form physical hydrogels of high toughness and self-healing. The random distribution of the opposite charges forms ionic bonds of a wide distribution of strength. The strong bonds serve as permanent cross-links, imparting elasticity, whereas the weak bonds serves as reversible sacrificial bonds by breaking and reforming to dissipate energy. In this work, we focus on the rupture behaviors of the polyampholyte physical hydrogel, P(NaSS-co-MPTC), copolymerized from sodium p-styrenesulfonate (NaSS) and 3-(methacryloylamino)propyltrimethylammonium chloride (MPTC). Tensile test and pure shear test were performed at various stretch rates in the viscoelastic responses region of the material. Tensile test showed yielding, strain softening, and strain hardening, revealing the dually cross-linked feature of the gel. Pure shear test showed crack blunting at the notched tip and a large yielding zone with butterfly shaped birefringence pattern ahead of the crack tip. After blunting, crack advanced at steady-state velocity with a constant angle. The conditions for the occurrence of crack blunting and variables governing the crack advancing angle are discussed. We found that even for these highly stretchable samples, significant blunting only occurs when the tensile fracture stress σf is larger than modulus E by a factor of about 2, in consistent with Hui’s theoretical prediction for elastic materials. The crack advancing angle θ was found to be proportional to σy/E over a wide stretch rate range, where σy is the yielding stress. In addition, the fracture energy was correlated to small strain modulus by a power law in the viscoelastic response region. This systematic study will merit revealing the fracture mechanism of tough viscoelastic materials including biological tissues and recently developed tough and highly stretchable hydrogels

In examining adsorption of a few selected single amino acids on Au and Pd cluster models by density functional theory calculations, we have shown that specific side-chain binding affinity to the surface may occur because of a combination of effects, including charge transfer. Larger binding was calculated at the Pd interface. In addition, the interplay between amino acid solvation and adsorption at the interface was considered from first principles. This analysis serves as the first step toward gaining a more accurate understanding of specific interactions at the interface of biological-metal nanostructures than has been attempted in the past.

The redox potentials and reorganization energies of the type 1 (T1) Cu site in four multicopper oxidases were calculated by combining first principles density functional theory (QM) and QM/MM molecular dynamics (MD) simulations. The model enzymes selected included the laccase from Trametes versicolor, the laccase-like enzyme isolated from Bacillus subtilis, CueO required for copper homeostasis in Escherichia coli, and the small laccase (SLAC) from Streptomyces coelicolor. The results demonstrated good agreement with experimental data and provided insight into the parameters that influence the T1 redox potential. Effects of the immediate T1 Cu site environment, including the His(N(δ))-Cys(S)-His(N(δ)) and the axial coordinating amino acid, as well as the proximate H(N)(backbone)-S(Cys) hydrogen bond, were discerned. Furthermore, effects of the protein backbone and side-chains, as well as of the aqueous solvent, were studied by QM/MM molecular dynamics (MD) simulations, providing an understanding of influences beyond the T1 Cu coordination sphere. Suggestions were made regarding an increase of the T1 redox potential in SLAC, i.e., of Met198 and Thr232 in addition to the axial amino acid Met298. Finally, the results of this work presented a framework for understanding parameters that influence the Type 1 Cu MCO redox potential, useful for an ever-growing range of laccase-based applications.

The zerovalent bis(η6-benzene) f-metal sandwich complexes M(C6H6)2 (M = La, Ce, Nd, Gd, Tb, Lu, Th, U) were investigated with state-of-the-art quantum chemical ab initio approaches taking into account the effects of electron correlation and relativity. Ground state assignments, optimized metal−ring distances, symmetric metal−ring stretching frequencies, and metal−ring bonding energies are reported. The effects of ring substitution on the metal−ring binding energies are discussed. The complexes of Th and U are predicted to be at least as stable as the corresponding lanthanide systems and form possible synthetic targets. Whereas the lanthanide systems have a 4f n ground state configuration (n = 1, 3 for Ce, Nd), the corresponding actinide compounds should possess, as a consequence of stronger relativistic effects, a 5f n -1 ground state configuration, with a possible strong admixture of 5f n -1 (n = 1, 3 for Th, U). The back-donation from the occupied metal d± 2 to the empty π orbitals of the benzene ligands is found to be the dominant bonding interaction. Whereas the lanthanide 4f orbitals are essentially localized on the metals and chemically inactive, the actinide 5f shell is partially delocalized and its f± 2 components may also take part in the back-donation.