Optimization of Crystal Structures of Archetypical Pharmaceutical Compounds: A Plane-Wave DFT-D Study Using Quantum Espresso

Abstract

Previously, it was shown that crystal structure prediction based on genetic algorithms (MGAC program) coupled with force field methods could consistently find experimental structures of crystals. However, inaccuracies in the force field potentials often resulted in poor energetic ranking of the experimental structure, limiting the usefulness of the method. In this work, dispersion-corrected density functional theory is employed to improve the accuracy of the energy rankings, using the software package Quantum Espresso. The best choices of running parameters for this application were determined, followed by completion of crystal optimizations on a test set of archetypical pharmaceutical molecules. It is shown here that the variable cell optimization of experimental structures reproduces the experimental structure with high accuracy (RMS < 0.5 Å) for this test set. It is also shown that the use of electronic structure theory based methods greatly improves the energetic ranking of structures produced by MGAC when used with a force field method, such that the experimental match is found with a high degree of accuracy.

Crystal structure prediction from first principles: The crystal structures of glycine

“…30 These three experimental structures were locally optimized using the QE vc-relax option, which allows for optimization of the unit cell parameters along with all atomic coordinates, with the same QE parameters used in our previous work (see below). 18 In all cases the experimental structures converged to local minima in close proximity to the experimental structures. The QE energies for these local minima structures are E α-glycine = −147,662.07 kJ/mol, E β-glycine = −147,659.78 kJ/mol, and E γ-glycine = −147,663.10 kJ/mol, which reproduce the experimental stability order: γ-glycine > α-glycine > β-glycine.…”

“…al . 18 The DFT functional used was the Perdew-Burke-Ernzerhof generalized gradient approximation. 32 The dispersion correction method selected was the semi-empirical D2 method proposed by Grimme as implemented in Quantum Espresso.…”

“…Our more recent work 18 has demonstrated that when using Quantum Espresso (QE) to locally optimize the experimental structures in the K&P set the calculated local minima structure compares well with the experimental structure in all 32 of the molecules, with RMS differences ranging from 0.056 to 0.459 Å. This implies that for unknown structures, an approach which couples the use of MGAC with energy evaluation using QE will be successful in finding the “true” experimental structures.…”

“…We have recently demonstrated, 18 using a set of drug like molecules, that local optimization using full DFT-D results in near experimental structures only when the starting point is quite close to the experimental one. Therefore global optimization with a reliable and universal energy function is necessary for accurate CSP.…”

Structural and electronic properties of the iron pnictide compound EuFe2As2 from first principles

“…The PAW Non Linear Correction Pseudo Potentials were used in these calculations [29][30][31][32][33]. Before running the Self-Consistent Calculations, the Variable Cell relax( vc-relax )calculation was performed to obtain relaxed atomic positions and then optimization of cell dimensions, K-points, and the kinetic energy cut off was also done so as to obtain a relaxed crystal structure, to ensure that the ground state crystal structure is obtained and that the results are free from stress [8,[34][35][36]. The initial k-point sampling was done using p , a 2 where a is the lattice parameter [19].…”