Transferable Neural Network Potential Energy Surfaces for Closed-Shell Organic Molecules: Extension to Ions

Transferable high dimensional neural network potentials (HDNNP) have shown great promise as an avenue to increase the accuracy and domain of applicability of existing atomistic force fields for organic systems relevant to life science. We have previously reported such a potential (Schrödinger-ANI) that has broad coverage of druglike molecules. We extend that work here to cover ionic and zwitterionic druglike molecules expected to be relevant to drug discovery research activities. We report a novel HDNNP architechture, which we call QRNN, that predicts atomic charges and uses these charges as descriptors in an energy model which delivers conformational energies within chemical accuracy when measured against the reference theory it is trained to. Further, we find that delta learning based on a semi-empirical level of theory approximately halves the errors. We test the models on torsion energy profiles, relative conformational energies, geometric parameters and relative tautomer errors.

The interrelation between the structural, electronic and energy parameters of nitrogen inversion in ammonia derivatives

The structural, electronic and energy parameters in the ground and transition states of inversion of the amines H2NXHn (XHn=CH3, NH2, OH, F, SiH3, PH2, SH, and Cl) have been calculated by using DFT (PBE96/def2-tzvpp) method. It was established that the increase of electronegativity of the substituents (the X atoms within the same period) leads to stabilization of the ground and transition states of the molecules. The increase in the inversion barriers is due to relative stabilization of the ground states, but not due to relative destabilization of the transition states. The inversion barriers rise with a decrease in conformational energies of the substituents, sums of valence angles at the nitrogen atoms, negative charges on them, energies of the nitrogen lone pairs and with an increase in s-character and population of the nitrogen lone pairs and difference between the energies of the nitrogen lone pairs in the ground and transition states. The main parameters that allow predicting the change of the nitrogen inversion barriers, independently of the type or volume of the XHn substituent, are s-character of the nitrogen lone pairs and difference between the energies of the nitrogen lone pairs. In all other cases, the correlations were found only for the amines containing the elements of the same period at the nitrogen atom. All structural and electronic parameters of amines containing the Х atoms from the second period are more sensitive to the changes of the ХНn substituents than the parameters of amines containing the Х atoms from the third period.

Conformational energies and equilibria of cyclic dinucleotides in vacuo and in solution: computational chemistry vs. NMR experiments

Computational “error bars” for modelling cyclic dinucleotides – NMR experiment vs. quantum mechanics and molecular dynamics.

Theoretical study on conformational energies of transition metal complexes

Conformational energies are an important chemical property for which a performance assessment of theoretical methods is mandatory. Efficient low-cost methods are valuable for the generation and energetic ranking of conformers.

r2SCAN-3c: An Efficient “Swiss Army Knife” Composite Electronic-Structure Method

The recently proposed second revision of the SCAN meta-GGA density-functional approximation (DFA) {Furness et al., J. Phys. Chem. Lett. 2020, 11, 8208-8215, termed r²SCAN} is used to construct an efficient composite electronic-structure method termed r²SCAN-3c, expanding the "3c'' series (hybrid: HSE/PBEh-3c, GGA: B97-3c, HF: HF-3c) to themGGA level. To this end, the unaltered r²SCAN functional is combined with a tailor-made <br>triple-zeta Gaussian AO-basis as well as with refitted D4 and gCP corrections for London-dispersion and basis-set superposition error. The performance of the new method is evaluated for the GMTKN55 thermochemical database covering large parts of chemical space with about 1500 <br>data points, as well as additional benchmarks for noncovalent interactions, organometallic reactions, lattice energies of organic molecules and ices, as well as for the adsorption on polar salt and non-polar coinage-metal surfaces. These comprehensive tests reveal a spectacular performance and robustness of r²SCAN-3c for reaction energies and noncovalent interactions in molecular and periodic systems, as well as outstanding conformational energies, and consistent structures. At just one tenth of the cost, r²SCAN-3c provides one of the best results of all semi-local DFT/QZ methods ever tested for the GMTKN55 benchmark database. Specifically for reaction and conformational energies as well as for noncovalent interactions, the new method outperforms hybrid-DFT/QZ approaches, compared to which the computational savings are even larger (factor 100-1000).<br>In relation to other "3c'' methods, r²SCAN-3c by far surpasses the accuracy of its predecessor B97-3c at only about twice the cost. The perhaps most relevant remaining systematic deviation of r²SCAN-3c is due to self-interaction-error, owing to its mGGA nature. However, SIE is notably reduced compared to other (m)GGAs, as is demonstrated for several examples. After all, this remarkably efficient and robust method is chosen as our new group default, replacing previous low-level DFT and partially even expensive high-level methods in most standard applications for systems with up to several hundreds of atoms.<br><br>

r2SCAN-3c: An Efficient “Swiss Army Knife” Composite Electronic-Structure Method

The recently proposed second revision of the SCAN meta-GGA density-functional approximation (DFA) {Furness et al., J. Phys. Chem. Lett. 2020, 11, 8208-8215, termed r²SCAN} is used to construct an efficient composite electronic-structure method termed r²SCAN-3c, expanding the "3c'' series (hybrid: HSE/PBEh-3c, GGA: B97-3c, HF: HF-3c) to themGGA level. To this end, the unaltered r²SCAN functional is combined with a tailor-made <br>triple-zeta Gaussian AO-basis as well as with refitted D4 and gCP corrections for London-dispersion and basis-set superposition error. The performance of the new method is evaluated for the GMTKN55 thermochemical database covering large parts of chemical space with about 1500 <br>data points, as well as additional benchmarks for noncovalent interactions, organometallic reactions, lattice energies of organic molecules and ices, as well as for the adsorption on polar salt and non-polar coinage-metal surfaces. These comprehensive tests reveal a spectacular performance and robustness of r²SCAN-3c for reaction energies and noncovalent interactions in molecular and periodic systems, as well as outstanding conformational energies, and consistent structures. At just one tenth of the cost, r²SCAN-3c provides one of the best results of all semi-local DFT/QZ methods ever tested for the GMTKN55 benchmark database. Specifically for reaction and conformational energies as well as for noncovalent interactions, the new method outperforms hybrid-DFT/QZ approaches, compared to which the computational savings are even larger (factor 100-1000).<br>In relation to other "3c'' methods, r²SCAN-3c by far surpasses the accuracy of its predecessor B97-3c at only about twice the cost. The perhaps most relevant remaining systematic deviation of r²SCAN-3c is due to self-interaction-error, owing to its mGGA nature. However, SIE is notably reduced compared to other (m)GGAs, as is demonstrated for several examples. After all, this remarkably efficient and robust method is chosen as our new group default, replacing previous low-level DFT and partially even expensive high-level methods in most standard applications for systems with up to several hundreds of atoms.<br><br>

r2SCAN-3c: An Efficient “Swiss Army Knife” Composite Electronic-Structure Method

The recently proposed second revision of the SCAN meta-GGA density-functional approximation (DFA) {Furness et al., J. Phys. Chem. Lett. 2020, 11, 8208-8215, termed r²SCAN} is used to construct an efficient composite electronic-structure method termed r²SCAN-3c, expanding the "3c'' series (hybrid: HSE/PBEh-3c, GGA: B97-3c, HF: HF-3c) to themGGA level. To this end, the unaltered r²SCAN functional is combined with a tailor-made <br>triple-zeta Gaussian AO-basis as well as with refitted D4 and gCP corrections for London-dispersion and basis-set superposition error. The performance of the new method is evaluated for the GMTKN55 thermochemical database covering large parts of chemical space with about 1500 <br>data points, as well as additional benchmarks for noncovalent interactions, organometallic reactions, lattice energies of organic molecules and ices, as well as for the adsorption on polar salt and non-polar coinage-metal surfaces. These comprehensive tests reveal a spectacular performance and robustness of r²SCAN-3c for reaction energies and noncovalent interactions in molecular and periodic systems, as well as outstanding conformational energies, and consistent structures. At just one tenth of the cost, r²SCAN-3c provides one of the best results of all semi-local DFT/QZ methods ever tested for the GMTKN55 benchmark database. Specifically for reaction and conformational energies as well as for noncovalent interactions, the new method outperforms hybrid-DFT/QZ approaches, compared to which the computational savings are even larger (factor 100-1000).<br>In relation to other "3c'' methods, r²SCAN-3c by far surpasses the accuracy of its predecessor B97-3c at only about twice the cost. The perhaps most relevant remaining systematic deviation of r²SCAN-3c is due to self-interaction-error, owing to its mGGA nature. However, SIE is notably reduced compared to other (m)GGAs, as is demonstrated for several examples. After all, this remarkably efficient and robust method is chosen as our new group default, replacing previous low-level DFT and partially even expensive high-level methods in most standard applications for systems with up to several hundreds of atoms.<br><br>