arXiv subjects

Valerie Vaissier Welborn

Publications and source records attributed to Valerie Vaissier Welborn.

4 recordsLinked to original sources

arXiv2020

The Critical Role of Thermal Fluctuations for Electrocatalytic Metal Surface Properties and CO Binding Trends

This work addresses a longstanding theoretical discrepancy using Density Functional Theory (DFT) with experimental observations of CO binding trends on electrocatalytically relevant metals for the CO2 reduction reaction (CO2RR). By introducing thermal fluctuations using appropriate statistical mechanical NVT and NPT ensembles, we show that DFT with universal dispersion interactions yields qualitatively better metal surface strain trends and CO binding energetics, consistently predicts the correct site preference for all metals due to thermally induced surface distortions that preferentially exposes the undercoordinated atop site for Cu(111) and Pt(111), and for the weak binding Ag(111) and Au(111) surfaces at finite temperatures shows CO-metal interactions that are a mixture of chemisorbed and physisorbed species. This study better places theory as an equal partner to experimental heterogeneous catalysis by demonstrating the need to fully account for finite temperature fluctuations to make contact with surface science experiments.

physics.chem-ph↗

arXiv2020

Drug design principles from electric field calculations: understanding SARS-CoV-2 main protease interaction with X77 non-covalent inhibitor

Fast and effective drug discovery processes rely on rational drug design to circumvent the tedious and expensive trial and error approach. However, accurate predictions of new remedies, which are often enzyme inhibitors, require a clear understanding of the nature and function of the key players governing the interaction between the drug candidate and its target. Here, we propose to calculate electric fields to explicitly link structure to function in molecular dynamics simulations, a method that can easily be integrated within the rational drug discovery workflow. By projecting the electric fields onto specific bonds, we can identify the system components that are at the origin of stabilizing intermolecular interactions (covalent and non-covalent) in the active site. This helps to significantly narrow the exploration space when predicting new inhibitors. To illustrate this method, we characterize the binding of the non-covalent inhibitor X77 to the main protease of SARS-CoV-2, a particularly time-sensitive drug discovery problem. With electric field calculations, we were able to identify 3 key residues (Asn-142, Met-165 and Glu-166), that have functional consequences on X77. This contrasts with the nearly 20 residues reported in previous studies as being in close contact with inhibitors in the active site of the protease. As a result, the search for new non-covalent inhibitors can now be accelerated by techniques that look to optimize the interaction between candidate molecules and these residues.

physics.bio-ph↗

arXiv2019

Interplay of Water and a Supramolecular Capsule for Catalysis of Reductive Elimination Reaction from Gold

Supramolecular assemblies have gained tremendous attention due to their apparent ability to catalyze reactions with the efficiencies of natural enzymes. Using Born-Oppenheimer molecular dynamics and density functional theory, we identify the origin of the catalytic power of the supramolecular assembly Ga$_4$L$_{612-}$ on the reductive elimination reaction from gold complexes and their similarity to enzymes. By comparing the catalyzed and uncatalyzed reaction in explicit solvent to identify the reaction free energies of the reactants, transition states, and products, we determine that a catalytic moiety -- an encapsulated water molecule -- generates electric fields that contribute significant reduction in the activation free energy. Although this is unlike the biomimetic scenario of catalysis through direct host-guest interactions, the nanocage host preconditions the transition state for greater sensitivity to electric field projections onto the breaking carbon bonds to complete the reductive elimination reaction with greater catalytic efficiency. However it is also shown that the nanocage poorly organizes the interfacial water, which in turn creates electric fields that misalign with the breaking bonds of the substrate, thus identifying new opportunities for catalytic design improvements in nanocage assemblies.

physics.chem-ph↗

arXiv2019

Fluctuations of Electric Fields in the Active Site of the Enzyme Ketosteroid Isomerase

We report the effect of conformational dynamics on the fluctuations of electric fields in the active site of the enzyme Ketosteroid Isomerase (KSI). While KSI is considered rigid with little conformational variation to support different stages of the catalytic cycle, we show that KSI utilizes cooperative side chain motions of the entire protein scaffold outside the active site, which contribute negligibly to the electric fields on the substrate, by progressively stabilizing electric field contributions by particular active site residues at different timescales. The design of synthetic enzymes could benefit from strategies that can take advantage of the dynamics by using electric fields fluctuations as a guide.

physics.chem-ph↗