Juan Manuel Ortiz-Sánchez

Electronic-structure and quantum dynamical study of the photochromism of the aromatic Schiff base salicylideneaniline

The ultrafast proton transfer dynamics of salicylideneaniline has been theoretically analyzed in the ground and first singlet excited electronic states using density functional theory (DFT) and time-dependent DFT calculations, which predict a (pi,pi( *)) barrierless excited state intramolecular proton transfer (ESIPT). In addition to this, the photochemistry of salicylideneaniline is experimentally known to present fast depopulation processes of the photoexcited species before and after the proton transfer reaction. Such processes are explained by means of conical intersections between the ground and first singlet (pi,pi( *)) excited electronic states. The electronic energies obtained by the time-dependent density functional theory formalism have been fitted to a monodimensional potential energy surface in order to perform quantum dynamics study of the processes. Our results show that the proton transfer and deactivation of the photoexcited species before the ESIPT processes are completed within 49.6 and 37.7 fs, respectively, which is in remarkable good agreement with experiments.

On the Role of Dewetting Transitions in Host–Guest Binding Free Energy Calculations

We use thermodynamic integration (TI) and explicit solvent molecular dynamics (MD) simulation to estimate the absolute free energy of host–guest binding. In the unbound state, water molecules visit all of the internally accessible volume of the host, which is fully hydrated on all sides. Upon binding of an apolar guest, the toroidal host cavity is fully dehydrated; thus, during the intermediate λ stages along the integration, the hydration of the host fluctuates between hydrated and dehydrated states. Estimating free energies by TI can be especially challenging when there is a considerable difference in hydration between the two states of interest. We investigate these aspects using the popular TIP3P and TIP4P water models. TI free energy estimates through MD largely depend on water-related interactions, and water dynamics significantly affect the convergence of binding free energy calculations. Our results indicate that wetting/dewetting transitions play a major role in slowing the convergence of free energy estimation. We employ two alternative approaches—one analytical and the other empirically based on actual MD sampling—to correct for the standard state free energy. This correction is sizable (up to 4 kcal/mol), and the two approaches provide corrections that differ by about 1 kcal/mol. For the system considered here, the TIP4P water model combined with an analytical correction for the standard state free energy provides higher overall accuracy. This observation might be transferable to other systems in which water-related contributions dominate the binding process.

Thermodynamic integration to predict host-guest binding affinities.

An alchemical free energy method with explicit solvent molecular dynamics simulations was applied as part of the blind prediction contest SAMPL3 to calculate binding free energies for seven guests to an acyclic cucurbit-[n]uril host. The predictions included determination of protonation states for both host and guests, docking pose generation, and binding free energy calculations using thermodynamic integration. We found a root mean square error (RMSE) of

Identification of potential small molecule binding pockets on Rho family GTPases.

3.6\,\hbox{kcal}\,\hbox{mol}^{-1}

Exploring the Photophysical Properties of Molecular Systems Using Excited State Accelerated ab Initio Molecular Dynamics.

from the reference experimental results, with an R2 correlation of 0.51. The agreement with experiment for the largest contributor to this error, guest 6, is improved by

Theoretical study on the excited-state intramolecular proton transfer in the aromatic schiff base salicylidene methylamine: an electronic structure and quantum dynamical approach.

1.7\,\hbox{kcal}\,\hbox{mol}^{-1}