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Proteins play diverse and vital roles in biology, which are dominated by their three-dimensional structures. The three-dimensional structure of a protein determines its functions and chemical properties. Protein secondary structures, including α-helices and β-sheets, are key components of the protein architecture. Molecular interactions, in particular hydrogen bonds, play significant roles in the formation of protein secondary structures. Precise and quantitative estimations of these interactions are required to understand the principles underlying the formation of three-dimensional protein structures. In the present study, we have investigated the molecular interactions in α-helices and β-sheets, using ab initio wave function-based methods, the Hartree-Fock method (HF) and the second-order Møller-Plesset perturbation theory (MP2), density functional theory, and molecular mechanics. The characteristic interactions essential for forming the secondary structures are discussed quantitatively.

Ancient conserved domain protein/cyclin M (CNNM) family proteins are evolutionarily conserved Mg(2+) transporters. However, their biochemical mechanism of action remains unknown. Here, we show the functional importance of the commonly conserved cystathionine-β-synthase (CBS) domains and reveal their unique binding ability to ATP. Deletion mutants of CNNM2 and CNNM4, lacking the CBS domains, are unable to promote Mg(2+) efflux. Furthermore, the substitution of one amino acid residue in the CBS domains of CNNM2, which is associated with human hereditary hypomagnesemia, abrogates Mg(2+) efflux. Binding analyses reveal that the CBS domains of CNNM2 bind directly to ATP and not AMP in a manner dependent on the presence of Mg(2+), which is inhibited in a similar pattern by the disease-associated amino acid substitution. The requirement of Mg(2+) for these interactions is a unique feature among CBS domains, which can be explained by the presence of highly electronegative surface potentials around the ATP binding site on CNNM2. These results demonstrate that the CBS domains play essential roles in Mg(2+) efflux, probably through interactions with ATP. Interactions with ATP, which mostly forms complexes with Mg(2+) in cells, may account for the rapid Mg(2+) transport by CNNM family proteins., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

A molecular dynamics (MD) simulation program for biological macromolecules was implemented with a non-Ewald scheme for long-ranged electrostatic interactions and run on a general purpose graphics processing unit (GPU). We recently developed several non-Ewald methods to compute the electrostatic energies with high precision. In particular, the zero-dipole summation (ZD) method, which takes into account the neutralities of charges and dipoles in a truncated subset, enables the calculation of electrostatic interactions with high accuracy and low computational cost, and its algorithm is simple enough to be implemented in a GPU. We developed an MD program with the space decomposition algorithm, myPresto/psygene, and applied it to several biological macromolecular systems with GPUs implementing the ZD method. Rapid computing performance with high accuracy was obtained.

Metal ions in proteins are important not only for the formation of the proper structures but also for various biological activities. For biological functions such as hydrolysis and oxidation, metal ions often adopt unusual coordination structures. We constructed a stable scaffold for metal binding to create distorted metal coordination structures. A stable four stranded alpha-helical coiled-coil structure was used as the scaffold, and the metal binding site was in the cavity created at the center of the structure. Two His residues and one Asp or Glu residue were used to coordinate the metal ions, AM2D and AM2E, respectively. Cu(2+) bound to AM2D with an equatorial planar coordination structure with two His, one Asp, and H(2)O as detected by electron spin resonance and UV spectral analyzes. On the other hand, Cu(2+) had a slightly distorted square planar structure when it bound two His and Glu in AM2E, due to the longer side-chain of the Glu residue as compared to the Asp residue. Computational analysis also supported the distorted coordination structure of Cu(2+) in AM2E. This construct should be useful to create various coordinations of metal ions for catalytic functions., (2009 Wiley Periodicals, Inc.)

The electronic structure and magnetic interactions of the active site of sweet potato purple acid phosphatase (PAP) were investigated by using UHF, pure DFT (UBLYP), and hybrid DFT methods (UB3LYP and UB2LYP). PAP catalyzes the hydrolysis of a phosphate ester under acidic conditions and contains a binuclear metal center. Sweet potato PAP provides stronger antiferromagnetic coupling than other PAPs. UB3LYP showed reasonably good agreement with the experimental magnetic coupling, indicating that this stronger antiferromagnetic coupling is caused by a mu-oxo bridge in the Fe(III)-Mn(II) binuclear metal center, which is the origin of the asymmetric spin delocalization. The type of bridging ligand is essential for the reaction mechanism, because the bridging ligand is suggested to function as a nucleophile in the reaction. Analyses of the natural orbital and spin density distributions implied the asymmetric spin delocalization on the bridging oxygen. The mechanism and the pathway of the antiferromagnetic coupling between Fe(III) and Mn(II) were discussed, using chemical indices introduced with the occupation numbers of singly occupied natural orbitals.

We have investigated the decomposition pathway of dioxetanones 1c with a phenoxide anion group by the B3LYP/6-31+G(d) method together with the second-order multireference Møller-Plesset perturbation (MRMP) theory and propose charge-transfer-induced luminescence (CTIL) with polarization-induced branching excitation processes. In the gas phase, the thermal decomposition of 1c occurs by an asynchronous two-stage pathway without a discrete intermediate; that is, the initial O-O bond breaking to generate a charge-transfer (CT) diradical species is immediately followed by the subsequent C-C bond breaking with simultaneous back CT, which is responsible for the surface crossing at the avoided crossing. The activation energy is dramatically reduced from 19.4 to 3.8 kcal mol(-)(1) by the deprotonation of phenol meta-1d to its anion meta-1c, showing an important role of the endothermic CT. The odd/even selection rule for the chemiluminescence efficiency can be explained by the orbital interaction for the back CT between the carbonyl pi orbital and either a HOMO or a LUMO of the generated light emitters. To examine the accessibility of the chemically initiated electron exchange luminescence (CIEEL) route, we considered the solvent effects on the free-energy change of meta-1c by using continuum solvent models. The bending vibration mode of the CO(2) fragment is specifically considered. Borderline features emerges from the solution-phase CT reaction of meta-1c, which depends on the solvent polarity: one is a nonadiabatic or adiabatic back CT process (polarization-induced concerted CTIL), and the other is a radical dissociation, i.e., complete one-electron-transfer process (CIEEL).

The conductor-like polarizable continuum model (CPCM) using several cavity models is applied to compute aqueous solvation free energies for a number of organic molecules (30 neutral molecules, 21 anions, and 19 cations). The calculated solvation free energies are compared to the available experimental data from the viewpoint of cavity models, computational methods, calculation time, and aqueous pKa values. The HF/6-31+G(d)//HF/6-31+G(d) and the HF/6-31+G(d)//B3LYP/6-31+G(d) with the UAKS cavities, in which radii are optimized with PBE0/6-31G(d), provide aqueous solvation effects in best agreement with available experimental data. The mean absolute deviations from experiment are 2.6 kcal/mol. The MP2/6-31++G(d,p)//HF/6-31+G(d) with the CPCM-UAKS(HF/6-31+G(d)) calculation is also performed for the base-catalyzed hydrolysis of methyl acetate in water.

The phenalenyl radical (1) is a prototype of the hydrocarbon radical. Recently, the single crystal of 2,5,8-tri-tert-butylphenalenyl (2) was isolated and showed that the two phenalenyl radicals form a staggered dimeric pair, giving rise to strong antiferromagnetic interactions. The origin of the antiferromagnetic interactions and the nature of the chemical bond for the dimeric pair are challenging issues for chemists. First, spin-polarized hybrid DFT (Becke's half and half LYP (UB2LYP)) and CASSCF calculations were performed for 2 and its simplified model, the staggered-stacking phenalenyl radical dimeric pair (3a), to elucidate the origin of the strong antiferromagnetic coupling and the characteristics of the chemical bond. The calculated results showed that a SOMO-SOMO overlap effect was responsible for the strong antiferromagnetic interactions and weak or intermediate covalent bonding between phenalenyl radicals. The tert-butyl groups introduced at three beta-positions hardly affected the magnetic coupling, mainly causing steric hindrances in the crystalline state. Next, to obtain insight into ferromagnetic stacking, we investigated the stacking effect of staggered (3a)- and eclipsed (3b)-stacking phenalenyl radical dimeric pairs with a change of the SOMO-SOMO overlap on the basis of the extended McConnell model. We found that the stacking mode of the dimeric pair with both a small SOMO-SOMO overlap and a ferromagnetic spin polarization effect provided a ferromagnetic coupling.