Jordi Villà

Multiconfiguration molecular mechanics algorithm for potential energy surfaces of chemical reactions

We present an efficient algorithm for generating semiglobal potential energy surfaces of reactive systems. The method takes as input molecular mechanics force fields for reactants and products and a quadratic expansion of the potential energy surface around a small number of geometries whose locations are determined by an iterative process. These Hessian expansions might come, for example, from ab initio electronic structure calculations, density functional theory, or semiempirical molecular orbital theory. A 2×2 electronic diabatic Hamiltonian matrix is constructed from these data such that, by construction, the lowest eigenvalue of this matrix provides a semiglobal approximation to the lowest electronically adiabatic potential energy surface. The theory is illustrated and tested by applications to rate constant calculations for three gas-phase test reactions, namely, the isomerization of 1,3-cis-pentadiene, OH+CH4→H2O+CH3, and CH2Cl+CH3F→CH3Cl+CH2F.

Simulations of ion current in realistic models of ion channels: The KcsA potassium channel

Realistic studies of ion current in biologic channels present a major challenge for computer simulation approaches. All‐atom molecular dynamics simulations involve serious time limitations that prevent their use in direct evaluation of ion current in channels with significant barriers. The alternative use of Brownian dynamics (BD) simulations can provide the current for simplified macroscopic models. However, the time needed for accurate calculations of electrostatic energies can make BD simulations of ion current expensive. The present work develops an approach that overcomes some of the above challenges and allows one to simulate ion currents in models of biologic channels. Our method provides a fast and reliable estimate of the energetics of the system by combining semimacroscopic calculations of the self‐energy of each ion and an implicit treatment of the interactions between the ions, as well as the interactions between the ions and the protein‐ionizable groups. This treatment involves the use of the semimacroscopic version of the protein dipole Langevin dipole (PDLD/S) model in its linear response approximation (LRA) implementation, which reduces the uncertainties about the value of the protein “dielectric constant.” The resulting free energy surface is used to generate the forces for on‐the‐fly BD simulations of the corresponding ion currents. Our model is examined in a preliminary simulation of the ion current in the KcsA potassium channel. The complete free energy profile for a single ion transport reflects reasonable energetics and captures the effect of the protein‐ionized groups. This calculated profile indicates that we are dealing with the channel in its closed state. Reducing the barrier at the gate region allows us to simulate the ion current in a reasonable computational time. Several limiting cases are examined, including those that reproduce the observed current, and the nature of the productive trajectories is considered. The ability to simulate the current in realistic models of ion channels should provide a powerful tool for studies of the biologic function of such systems, including the analysis of the effect of mutations, pH, and electric potentials. Proteins 2002;47:265–280.

Understanding the activation energy trends for the C2H4+OH→C2H4OH reaction by using canonical variational transition state theory

The potential-energy hypersurface of the addition reaction OH+C2H4 was partially explored following two different approaches. First, the stationary points were located at the MP2(FULL)/6-31G(d,p) level and then the minimum energy path (MEP) was built starting from the MP2 saddle-point geometry. In order to improve the energetics along the MEP, single-point calculations were carried out at several higher levels, in particular, PMP2, MP4sdtq, PMP4sdtq, and QCIsd(t). In a different approach, the C–O bond length was assumed to provide an accurate parametrization of the reaction path in the vicinity of the transition state. The minimum energy structures at the MP4sdq/6-311+G(d,p) level for 16 points along the RC–O coordinate have been calculated, followed by a generalized normal-mode analysis at the MP2(FULL)/6-311+G(d,p) level for each point. The initial potential information from both approaches was used to calculate canonical variational transition state (CVT) association rate constants for the temperature ...

Effective way of modeling chemical catalysis: Empirical valence bond picture of role of solvent and catalyst in alkylation reactions

A general methodology for the study of chemical catalysis is presented and demonstrated in a study of Friedel–Crafts‐type alkylation reactions that are constrained to collinear configurations. Ab initio potential energy surfaces in solution and relevant experimental results are used to calibrate general empirical valence bond (EVB) potential surfaces for studies of such reactions. The EVB surfaces allow one to interpolate the ab initio results to studies of the effect of different solvents, substituents, and catalysts on the alkylation reactions. This implicit approach introduces such effects by shifting the diagonal energies of the corresponding resonance structures. Such an EVB/shift approach appears valuable for assessing the effects of different catalysts and solvents on complex chemical reactions.

On the interpolation of the frequencies of vibrational modes in variational transition state calculations: an adiabatic or diabatic scheme?

The convenience of a diabatic or an adiabatic interpolation of frequencies in variational transition state calculations involving interpolation methodologies is discussed. The gas phase proton transfer between butanone and a hydroxide anion has been used to illustrate the theoretical discussion. For example, it has been shown that if vibrational normal mode crossings exist the simple adiabatic interpolation can produce incorrect entropy contributions and, as a consequence, a spurious displacement of the generalized transition state.