Design of intrinsically disordered proteins that undergo phase transitions with lower critical solution temperatures

Many naturally occurring elastomers are intrinsically disordered proteins (IDPs) built up of repeating units and they can demonstrate two types of thermoresponsive phase behavior. Systems characterized by lower critical solution temperatures (LCST) undergo phase separation above the LCST whereas systems characterized by upper critical solution temperatures (UCST) undergo phase separation below the UCST. There is congruence between thermoresponsive coil-globule transitions and phase behavior whereby the theta temperatures above or below which the IDPs transition from coils to globules serve as useful proxies for the LCST / UCST values. This implies that one can design sequences with desired values for the theta temperature with either increasing or decreasing radii of gyration above the theta temperature. Here, we show that the Monte Carlo simulations performed in the so-called intrinsic solvation (IS) limit version of the temperature-dependent ABSINTH implicit solvation model, yields a useful heuristic for discriminating between sequences with known LCST versus UCST phase behavior. Accordingly, we use this heuristic in a supervised approach, integrate it with a genetic algorithm, combine this with IS limit simulations, and demonstrate that novel sequences can be designed with LCST phase behavior. These calculations are aided by direct estimates of temperature dependent free energies of solvation for model compounds that are derived using the polarizable AMOEBA forcefield. To demonstrate the validity of our designs, we calculate coil-globule transition profiles using the full ABSINTH model and combine these with Gaussian Cluster Theory calculations to establish the LCST phase behavior of designed IDPs.

Calculation of VS,max and Its Use as a Descriptor for the Theoretical Calculation of pKa Values for Carboxylic Acids

The theoretical calculation of pKa values for Brønsted acids is a challenging task that involves sophisticated and time-consuming methods. Therefore, heuristic approaches are efficient and appealing methodologies to approximate these values. Herein, we used the maximum surface electrostatic potential (VS,max) on the acidic hydrogen atoms of carboxylic acids to describe the H-bond interaction with water (the same descriptor that is used to characterize σ-bonded complexes) and correlate the results with experimental pKa values to obtain a predictive model for other carboxylic acids. We benchmarked six different methods, all including an implicit solvation model (water): Five density functionals and the Møller–Plesset second order perturbation theory in combination with six different basis sets for a total of thirty-six levels of theory. The ωB97X-D/cc-pVDZ level of theory stood out as the best one for consistently reproducing the reported pKa values, with a predictive power of 98% correlation in a test set of ten other carboxylic acids.

Assessment of Constant-Potential Implicit Solvation Calculations of Electrochemical Energy Barriers for H2 evolution on Pt

Theoretical estimation of the activation energy of electrochemical reactions is of critical importance but remains challenging. In this work, we address the usage of an implicit solvation model for describing hydrogen evolution reaction steps on Pt(111) and Pt(110), and compare with the `extrapolation' approach as well as single-crystal measurements. We find that both methods yield qualitatively similar results, which are in fair agreement with the experimental data. Care should be taken, however, in addressing spurious electrostatic interactions between periodically repeated slabs in the VASPsol implementation. Considering the lower computational cost and higher flexibility of the implicit solvation approach, we expect this method to become a valuable tool in electrocatalysis.<br>

Assessment of Constant-Potential Implicit Solvation Calculations of Electrochemical Energy Barriers for H2 evolution on Pt

Theoretical estimation of the activation energy of electrochemical reactions is of critical importance but remains challenging. In this work, we address the usage of an implicit solvation model for describing hydrogen evolution reaction steps on Pt(111) and Pt(110), and compare with the `extrapolation' approach as well as single-crystal measurements. We find that both methods yield qualitatively similar results, which are in fair agreement with the experimental data. Care should be taken, however, in addressing spurious electrostatic interactions between periodically repeated slabs in the VASPsol implementation. Considering the lower computational cost and higher flexibility of the implicit solvation approach, we expect this method to become a valuable tool in electrocatalysis.<br>

Assessment of Constant-Potential Implicit Solvation Calculations of Electrochemical Energy Barriers

Theoretical estimation of the activation energy of electrochemical reactions is of critical importance but remains challenging. In this work, we address the usage of an implicit solvation model for describing hydrogen evolution reaction steps on Pt(111) and Pt(110), and compare with the `extrapolation' approach and co-workers as well as single-crystal measurements. We find that both methods yield qualitatively similar results, which are in fair agreement with the experimental data. Care should be taken, however, in addressing spurious electrostatic interactions between periodically repeated slabs in the VASPsol implementation. Considering the lower computational cost and higher flexibility of the implicit solvation approach, we expect this method to become a valuable tool in electrocatalysis.<br>