The hydrolysis reaction of guanosine triphosphate (GTP) by p21(ras) (Ras) has been modeled by using the ab initio type quantum mechanical-molecular mechanical simulations. Initial geometry configurations have been prompted by atomic coordinates of the crystal structure (PDBID: 1QRA) corresponding to the prehydrolysis state of Ras in complex with GTP. Multiple searches of minimum energy geometry configurations consistent with the hydrogen bond networks have been performed, resulting in a series of stationary points on the potential energy surface for reaction intermediates and transition states. It is shown that the minimum energy reaction path is consistent with an assumption of a two-step mechanism of GTP hydrolysis. At the first stage, a unified action of the nearest residues of Ras and the nearest water molecules results in a substantial spatial separation of the gamma-phosphate group of GTP from the rest of the molecule (GDP). This phase of hydrolysis process proceeds through the low barrier (16.7 kcal/mol) transition state TS1. At the second stage, the inorganic phosphate is formed in consequence of proton transfers mediated by two water molecules and assisted by the Gln61 residue from Ras. The highest transition state at this segment, TS3, is estimated to have an energy 7.5 kcal/mol above the enzyme-substrate complex. The results of simulations are compared to the previous findings for the GTP hydrolysis in the Ras-GAP (p21(ras)-p120(GAP)) protein complex. Conclusions of the modeling lead to a better understanding of the anticatalytic effect of cancer causing mutation of Gln61 from Ras, which has been debated in recent years.

We present a comprehensive theoretical analysis for the low-lying isomeric structures, energetics, and vibrational properties of dinuclear aluminum oxides Al2On (n=1–4) to aid interpretation of experimental spectroscopic data for these species. We also carried out natural population and natural bond orbital (NBO) analysis of the correlated and uncorrelated ab initio wave functions in order to elucidate the general bonding principles governing these species. We find that the equilibrium structures generally exhibit high ionic character (viz., effective Al3+ and O2− ionic units), but with significant modifications due to covalency, which is generally enhanced by electron correlation. Although certain previous experimental assignments are confirmed by our studies, in other cases the theoretical results strongly contradict suggested assignments. For a significant number of the reported experimental lines, we currently have no good theoretical candidate species.

A dynamical approach is proposed to discriminate between reactive (rES) and nonreactive (nES) enzyme-substrate complexes taking the SARS-CoV-2 main protease (Mpro) as an important example. Molecular dynamics simulations with the...

The energy profiles for the reaction OH -+ CO 2 f HCO 3are analyzed following the results of calculations carried out using both a continuum solvation model and a cluster approach. The minimum energy path, computed with the quantum chemistry LMP2 and B3LYP approximations, corresponds to the activation-less process in the gas phase but shows a barrier on the way from the reactants to the product in the dielectric continuum medium. In the cluster approach, the reacting species were completely surrounded by 30 water molecules, each considered as an effective fragment potential (EFP) acting on the quantum system. Positions of all particles were optimized along the reaction coordinate in this quantum mechanical-molecular mechanical (QM/MM) approximation. The energy profile obtained with the QM/MM(EFP) approach is in remarkable agreement with the results of the continuum model, showing the barrier in the same region. An analysis of the arrangements of the water molecules around the reacting species, as well as changes in geometry configurations and electronic distributions of the solute species, allows us to conclude that on the segment of the reaction path close to the potential barrier a considerable fraction of the negative charge on OHtransfers to CO 2 , accompanied by a sharp bending of the O-C-O species. As a result, the hydroxide anion loses water molecules from its hydration shell. We show that the height of the barrier on the free energy curve for the reaction OH -+ CO 2 f HCO 3in water can be estimated within the limits 8-13 kcal/mol, and its precise quantity depends on the reference value of experimental free energy of solvation of OH -.

We present the results of high-level electronic structure and dynamics simulationsof the photoactive protein Dreiklang. With the goal to understand the details ofDreiklang's photocycle, we carefully characterize the excited states of the ON-andOFF-forms of Dreiklang. The key ?nding of our study is the existence of a lowlyingexcited state of a charge-transfer (CT) character in the neutral ON form andthat population of this state, which is nearly isoenergetic with the locally excited(LE) bright state, initiates series of steps ultimately leading to the formation ofthe hydrated dark chromophore (OFF state). These results allow us to re?ne themechanistic picture of the Dreiklang's photocycle and photoactivation. File list (3) download file view on ChemRxiv dreiklang_paper_draft.pdf (2.19 MiB) download file view on ChemRxiv dreiklang_si_draft.pdf (3.21 MiB) download file view on ChemRxiv Dreiklang-hydration.zip (15.42 MiB)

Vibrational predissociation dynamics of ArHF and ArDF complexes is investigated theoretically for the first time owing to the use of three-dimensional potential energy surfaces (PES’s) based on the diatomics-in-molecule approach [J. Chem. Phys. 104, 5510 (1996)]. The original PES is improved empirically to yield a reasonable description of the lowest vibrational energy levels of the ArHF complex at J=0. Predissociation dynamics is studied by means of line shape and diabatic Fermi Golden Rule methods. The latter is found to provide excellent results for the total decay widths but only a qualitative estimate for the product rotational distributions. It is shown that predissociation dynamics is governed by vibrational to rotational energy transfer. The decay proceeds almost entirely into the highest accessible rotational product channel. This propensity manifests itself in the decrease of the predissociation lifetime upon increasing vibrational excitation of the diatomic fragment when the highest rotational channel appears to be closed. Another source of state specificity in the vibrational predissociation is the anisotropy of the PES. Absolute calculated lifetime values are likely too small, but exhibit some qualitative trends observed experimentally.

The quantum mechanical-molecular mechanical (QM/MM) theory was applied to calculate accurate structural parameters, vibrational and optical spectra of bathorhodopsin (BATHO), one of the primary photoproducts of the functional cycle of the visual pigment rhodopsin (RHO), and to characterize reaction routes from RHO to BATHO. The recently resolved crystal structure of BATHO (PDBID: 2G87) served as an initial source of coordinates of heavy atoms. Protein structures in the ground electronic state and vibrational frequencies were determined by using the density functional theory in the PBE0/cc-pVDZ approximation for the QM part and the AMBER force field parameters in the MM part. Calculated and assigned vibrational spectra of both model protein systems, BATHO and RHO, cover three main regions referring to the hydrogen-out-of-plan (HOOP) motion, the C==C ethylenic stretches, and the C--C single-bond stretches. The S(0)-S(1) electronic excitation energies of the QM part, including the chromophore group in the field of the protein matrix, were estimated by using the advanced quantum chemistry methods. The computed structural parameters as well as the spectral bands match perfectly the experimental findings. A structure of the transition state on the S(0) potential energy surface for the ground electronic state rearrangement from RHO to BATHO was located proving a possible route of the thermal protein activation to the primary photoproduct.

Infrared laser jet spectroscopy of transition metal hexacarbonylrare gas dimersThe conjecture that limited basis diatomics-in-molecules type potentials may serve as an accurate representation of many-body interactions is explored through molecular dynamics simulations of Ar n HF ͑nϭ1-12,62͒. The important ingredient in the constructed potentials is the inclusion of ionic configurations of HF. Once the admixture between ionic and covalent configurations is calibrated by reference to an ab initio surface of the ArHF dimer, a single three-body potential energy surface is defined, and used in subsequent simulations of larger clusters. The vibrational frequencies of HF, which are computed from velocity-velocity autocorrelation functions, quantitatively reproduce the cluster size dependent redshifts.