Habiburrahman Zulfikri

Introducing QMC/MMpol: Quantum Monte Carlo in Polarizable Force Fields for Excited States

We present for the first time a quantum mechanics/molecular mechanics scheme which combines quantum Monte Carlo with the reaction field of classical polarizable dipoles (QMC/MMpol). In our approach, the optimal dipoles are self-consistently generated at the variational Monte Carlo level and then used to include environmental effects in diffusion Monte Carlo. We investigate the performance of this hybrid model in describing the vertical excitation energies of prototypical small molecules solvated in water, namely, methylenecyclopropene and s-trans acrolein. Two polarization regimes are explored where either the dipoles are optimized with respect to the ground-state solute density (polGS) or different sets of dipoles are separately brought to equilibrium with the states involved in the electronic transition (polSS). By comparing with reference supermolecular calculations where both solute and solvent are treated quantum mechanically, we find that the inclusion of the response of the environment to the excitation of the solute leads to superior results than the use of a frozen environment (point charges or polGS), in particular, when the solute-solvent coupling is dominated by electrostatic effects which are well recovered in the polSS condition. QMC/MMpol represents therefore a robust scheme to treat important environmental effects beyond static point charges, combining the accuracy of QMC with the simplicity of a classical approach.

Multiple-Resonance Local Wave Functions for Accurate Excited States in Quantum Monte Carlo

We introduce a novel class of local multideterminant Jastrow-Slater wave functions for the efficient and accurate treatment of excited states in quantum Monte Carlo. The wave function is expanded as a linear combination of excitations built from multiple sets of localized orbitals that correspond to the bonding patterns of the different Lewis resonance structures of the molecule. We capitalize on the concept of orbital domains of local coupled-cluster methods, which is here applied to the active space to select the orbitals to correlate and construct the important transitions. The excitations are further grouped into classes, which are ordered in importance and can be systematically included in the Jastrow-Slater wave function to ensure a balanced description of all states of interest. We assess the performance of the proposed wave function in the calculation of vertical excitation energies and excited-state geometry optimization of retinal models whose π → π* state has a strong intramolecular charge-transfer character. We find that our multiresonance wave functions recover the reference values of the total energies of the ground and excited states with only a small number of excitations and that the same expansion can be flexibly used at very different geometries. Furthermore, significant computational saving can also be gained in the orbital optimization step by selectively mixing occupied and virtual orbitals based on spatial considerations without loss of accuracy on the excitation energy. Our multiresonance wave functions are therefore compact, accurate, and very promising for the calculation of multiple excited states of different character in large molecules.

Computational exploration of optical and functional properties of biorelevant photoswitches

Developing molecular photoswitches for applications in material science and biology is a very active research in chemistry. Photoswitches are a class of small molecular machines whose structures and properties can be switched between two states with light. In this dissertation, we contribute to better understand three biorelevant photoswitches using computational means. In Chapter 3, we develop a new class of wave functions within the accurate quantum Monte Carlo framework to explore the excited-state potential energy surfaces (PES). In constructing these wave functions, we employ multiple sets of localized active orbitals corresponding to the different Lewis resonance structures of the molecule. We also adopt the concept of orbitals domains of local coupled-cluster methods to select orbitals to correlate within an active space. Using retinal models as examples, we find that our novel and compact wave functions can be flexibly and accurately applied to very different parts of a PES. In Chapter 4, we embark on a journey to understand the complex photoswitching mechanism of donor-acceptor Stenhouse adducts (DASAs). At the density functional theory level, we are able to explain the available experimental data of photoswitching of two representative DASA molecules as regards the reversibility, the relative reaction rate on different solvents and the structure of the final products. Additionally, our multiconfigurational wave-function study shows that accounting for both static and dynamical electron correlation is necessary for an accurate excited-state PES. In Chapter 5, we focus our attention on understanding the very recent use of spiropyran photoswitch for drug-delivery applications. Photoswitching spiropyran covalently connected to subdomain IA of the human serum albumin protein was found to induce ligand release in the adjacent subdomain IB. Our molecular dynamics simulations demonstrate the allosteric nature of the interaction between the two subdomains induced by the photoswitch and provide an explanation of the factors regulating the ligand release.

Crystal Field in Rare-Earth Complexes: From Electrostatics to Bonding

The flexibility of first-principles (ab initio) calculations with the SO-CASSCF (complete active space self-consistent field theory with a treatment of the spin-orbit (SO) coupling by state interaction) method is used to quantify the electrostatic and covalent contributions to crystal field parameters. Two types of systems are chosen for illustration: 1) The ionic and experimentally well-characterized PrCl3 crystal; this study permits a revisitation of the partition of contributions proposed in the early days of crystal field theory; and 2) a series of sandwich molecules [Ln(ηn -Cn Hn )2 ]q , with Ln=Dy, Ho, Er, and Tm and n=5, 6, and 8, in which the interaction between LnIII and the aromatic ligands is more difficult to describe within an electrostatic approach. It is shown that a model with three layers of charges reproduces the electrostatic field generated by the ligands and that the covalency plays a qualitative role. The one-electron character of crystal field theory is discussed and shown to be valuable, although it is not completely quantitative. This permits a reduction of the many-electron problem to a discussion of the energy of the seven 4f orbitals.

Photoprogramming Allostery in Human Serum Albumin

Developing strategies to interfere with allosteric interactions in proteins not only promises to deepen our understanding of vital cellular processes but also allows their regulation using external triggers. Light is particularly attractive as a trigger being spatiotemporally selective and compatible with the physiological environment. Here, we engineered a hybrid protein in which irradiation with light opens a new allosteric communication route that is not inherent to the natural system. We select human serum albumin, a promiscuous protein responsible for transporting a variety of ligands in plasma, and show that by covalently incorporating a synthetic photoswitch to subdomain IA we achieve optical control of the ligand binding in subdomain IB. Molecular dynamics simulations confirm the allosteric nature of the interactions between IA and IB in the engineered protein. Specifically, upon illumination, photoconversion of the switch is found to correlate with a less-coordinated motion of the two subdomains and an increased flexibility of the binding pocket in subdomain IB, whose fluctuations are cooperatively enhanced by the presence of ligands, ultimately facilitating their release. Our combined experimental and computational work demonstrates how harnessing artificial molecular switches enables photoprogramming the allosteric regulation of binding activities in such a prominent protein.