A Direct, Quantitative Connection between Molecular Dynamics Simulations and Vibrational Probe Line Shapes.

A quantitative connection between molecular dynamics simulations and vibrational spectroscopy of probe-labeled systems would enable direct translation of experimental data into structural and dynamical information. To constitute this connection, all-atom molecular dynamics (MD) simulations were performed for two SCN probe sites (solvent-exposed and buried) in a calmodulin-target peptide complex. Two frequency calculation approaches with substantial nonelectrostatic components, a quantum mechanics/molecular mechanics (QM/MM)-based technique and a solvatochromic fragment potential (SolEFP) approach, were used to simulate the infrared probe line shapes.

Overcoming the Failure of Correlation for Out-of-Plane Motions in a Simple Aromatic: Rovibrational Quantum Chemical Analysis of c-CH.

Truncated, correlated, wave function methods either produce imaginary frequencies (in the extreme case) or nonphysically low frequencies in out-of-plane motions for carbon and adjacent atoms when the carbon atoms engage in π bonding. Cyclopropenylidene is viewed as the simplest aromatic hydrocarbon, and the present as well as previous theoretical studies have shown that this simple molecule exhibits this behavior in the two out-of-plane bends (OPBs). This nonphysical behavior has been treated by removing nearly linear dependent basis functions according to eigenvalues of the overlap matrix, by employing basis sets where the spd space saturatation is balanced with higher angular momentum functions, by including basis set superposition/incompleteness error (BSSE/BSIE) corrections, or by combining standard correlation methods with explicitly correlated methods to produce hybrid potential surfaces.

Communication: The failure of correlation to describe carbon=carbon bonding in out-of-plane bends.

Carbon-carbon multiply bonded systems are improperly described with standard, wave function-based correlation methods and Gaussian one-particle basis sets implying that thermochemical, spectroscopic, and potential energy surface computations are consistently erroneous. For computations of vibrational modes, the out-of-plane bends can be reported as imaginary at worst or simply too low at best. Utilizing the simplest of aromatic structures (cyclopropenylidene) and various levels of theory, this work diagnoses this known behavior as a combined one-particle and n-particle basis set effect for the first time.

Escherichia coli dihydrofolate reductase catalyzed proton and hydride transfers: temporal order and the roles of Asp27 and Tyr100.

The reaction catalyzed by Escherichia coli dihydrofolate reductase (ecDHFR) has become a model for understanding enzyme catalysis, and yet several details of its mechanism are still unresolved. Specifically, the mechanism of the chemical step, the hydride transfer reaction, is not fully resolved. We found, unexpectedly, the presence of two reactive ternary complexes [enzyme:NADPH:7,8-dihydrofolate (E:NADPH:DHF)] separated by one ionization event.

Probing the electrostatics of active site microenvironments along the catalytic cycle for Escherichia coli dihydrofolate reductase.

Electrostatic interactions play an important role in enzyme catalysis by guiding ligand binding and facilitating chemical reactions. These electrostatic interactions are modulated by conformational changes occurring over the catalytic cycle. Herein, the changes in active site electrostatic microenvironments are examined for all enzyme complexes along the catalytic cycle of Escherichia coli dihydrofolate reductase (ecDHFR) by incorporation of thiocyanate probes at two site-specific locations in the active site.

Calculation of vibrational shifts of nitrile probes in the active site of ketosteroid isomerase upon ligand binding.

The vibrational Stark effect provides insight into the roles of hydrogen bonding, electrostatics, and conformational motions in enzyme catalysis. In a recent application of this approach to the enzyme ketosteroid isomerase (KSI), thiocyanate probes were introduced in site-specific positions throughout the active site. This paper implements a quantum mechanical/molecular mechanical (QM/MM) approach for calculating the vibrational shifts of nitrile (CN) probes in proteins.

Molecular simulations of the structure and dynamics of water confined between alkanethiol self-assembled monolayer plates.

We have studied structural and dynamic properties of water confined between hydrophobic alkanethiol self-assembled monolayers (SAMs) using molecular-dynamics simulations. After quantifying the hydrophobic nature of the SAM surfaces via contact-angle calculations involving water droplets, we analyze the effect that the hydrophobic surfaces have on structural properties of the confined water such as density, tetrahedral ordering, orientational structure at the SAM-water interface, and on dynamical properties via calculation of diffusion coefficients. Both the SPC/E and TIP5P water models have been utilized in the calculations.

Theoretical study of the dynamics of F+alkanethiol self-assembled monolayer hydrogen-abstraction reactions.

The dynamics of the reactions of F atoms with octanethiol self-assembled monolayers (SAMs) has been studied using theoretical methods. F+SAM classical trajectories have been propagated directly using a quantum-mechanics (QM)/molecular-mechanics scheme in which the QM portion is described using a specific-reaction-parameters (SRP) semiempirical Hamiltonian. This SRP Hamiltonian has been derived using ab initio information of model gas-phase F+alkane reactions and its accuracy has been calibrated via comparison of the result of direct-dynamics calculations with available experiments on the F+CH(4)-->HF+CH(3) and F+C(2)H(6)-->HF+C(2)H(5) reactions.

Direct-dynamics study of the F + CH4, C2H6, C3H8, and i-C4H10 reactions.

We present a theoretical study of the dynamics of the first few members of the F + alkane --> HF + alkyl family of reactions (alkane = CH(4), C(2)H(6), C(3)H(8), and i-C(4)H(10)). Quasiclassical trajectories have been propagated employing a reparameterized semiempirical Hamiltonian that was derived in this work based on ab initio information of the global potential-energy surfaces of all reactions studied. The accuracy of the Hamiltonian is probed via comparison of the calculated dynamics properties with experimental results in the F + CH(4) --> HF + CH(3), F + CD(4) --> DF + CD(3), and F + C(2)H(6) --> HF + C(2)H(5) reactions.

Theoretical study of the dynamics of the H+CH4 and H+C2H6 reactions using a specific-reaction-parameter semiempirical Hamiltonian.

We present a theoretical study of the reactions of hydrogen atoms with methane and ethane molecules and isotopomers. High-accuracy electronic-structure calculations have been carried out to characterize representative regions of the potential-energy surface (PES) of various reaction pathways, including H abstraction and H exchange. These ab initio calculations have been subsequently employed to derive an improved set of parameters for the modified symmetrically-orthogonalized intermediate neglect of differential overlap (MSINDO) semiempirical Hamiltonian, which are specific to the H+alkane family of reactions.