Quantum Mechanics Using Psi4

Introduction

Psi4 is an open-source quantum chemistry package integrated into ICM for calculating molecular energies, optimizing molecular geometries, and assigning atomic partial charges. It is bundled with ICM and runs internally, so no separate installation or configuration is required.

The integration provides three main capabilities:

• Geometry optimization: Optimize molecular structures using density functional theory (DFT), including individual molecules, conformational stacks, and 3D chemicals in tables.
• Single-point energy calculation: Calculate the DFT energy of a molecular structure without changing its geometry.
• Atomic partial charge calculation: Calculate restrained electrostatic potential (RESP) charges by fitting atomic charges to the quantum electrostatic potential.

The default method for geometry optimization and energy calculation is B3LYP/6-31G*. Alternative functionals and basis sets can be specified via the command line. RESP charge calculations use HF/6-31G* by default.

ICM converts quantum energies from Hartree units to kcal/mol. For conformational stacks, or table entries sharing the same unique SMILES, energies are reported relative to the lowest-energy conformer.

Calculation time increases with molecular size and the size of the basis set. The number of CPU cores used is controlled by the nProc setting.

Quantum Geometry Optimization

The Minimize option performs a full quantum-mechanical geometry optimization using Psi4. It optimizes bond lengths, bond angles, and torsion angles using DFT.

To optimize a molecule:

1. Read a chemical structure into ICM.
2. Convert the chemical to a 3D ICM object.
3. Check that the atomic formal charges are correct, as these determine the total molecular charge.
4. Select MolMechanics/Quantum Mechanics/Minimize.

The default calculation method is B3LYP/6-31G*. During optimization, molecular energies and gradients are calculated and the geometry is adjusted to minimize the energy.

Optimization finishes when the convergence criteria for energy, forces, and displacement are satisfied, or when the maximum number of optimization steps is reached. The default maximum is 50 steps.

Energy units: Psi4 calculates energies in Hartree units. ICM converts these values to kcal/mol.

Command-line reference: minimize quantum.

Minimize/Evaluate Conformers

This option uses Psi4 to minimize or evaluate the energies of conformers stored in either a chemical table containing 3D structures or a molecular object with an embedded conformational stack.

To run the calculation:

1. Prepare a table of 3D conformers, for example using _confGen, or a molecular object with an embedded conformational stack.
2. For table input, ensure that hydrogen atoms are present. If using _confGen, disable the option to keep onlyheavy atoms.
3. Check that the atomic formal charges are correct.
4. Select MolMechanics/Quantum Mechanics/Minimize Evaluate Conformers from table and specify the input table or object (see different tabs at the top of the GUI dialog).
5. Choose whether to minimize the conformers or evaluate their energies only.

Each conformer is processed independently:

• Minimization optimizes the geometry of each conformer.
• Energy evaluation calculates the energy of each conformer without changing its geometry.

For a conformational stack, the results are stored back in the stack. For table input, energies are stored in the psi4_ey column.

Energies are expressed in kcal/mol, relative to the lowest-energy conformer within the stack or each group of table entries sharing the same unique SMILES.

Command-line references: minimize quantum and show energy quantum.

Quantum Torsion Scan

The Torsion Scan option calculates how molecular energy changes as a selected torsion angle is rotated. Conformations can be evaluated directly or optimized while keeping the scanned torsion fixed.

To perform a torsion scan:

1. Prepare a 3D ICM object and check that its atomic formal charges are correct.
2. Select the four atoms defining the torsion using the pick atom button, in order. The bond between the second and third atoms is the rotation axis.
3. Select MolMechanics/Quantum Mechanics/Torsion scan.
4. Specify the angular interval and scan range. For example, scanning from 0° to 360° at 15° intervals generates 25 conformations, including both endpoints. The 0° and 360° conformations represent the same torsion orientation.
5. Choose the number of cores you want to use

Energy Evaluation

Psi4 calculates the energy of each saved conformation using B3LYP/6-31G* by default, without further changing its geometry. Any relaxation during the initial generation of conformations depends on the torsion scan settings.

Minimization with a Fixed Torsion

Each conformation undergoes quantum geometry optimization while the scanned torsion remains fixed at its assigned angle. The remaining geometry is allowed to relax.

This option is slower than energy evaluation alone but can provide a more representative energy profile by allowing the molecule to adjust at each torsion angle.

Results

The conformations are stored in a conformational stack, with energies reported in kcal/mol relative to the lowest-energy conformation.

Command-line references: show energy quantum and minimize quantum (with fixed torsions).

Set Atomic Partial Charges

The Set Charges option calculates quantum-derived atomic partial charges and assigns them to the molecule in ICM. It uses the existing molecular conformation without minimizing or changing its geometry.

Charges are calculated using the RESP (Restrained Electrostatic Potential) method, which fits atomic partial charges to the quantum-mechanical electrostatic potential. The default calculation level is HF/6-31G*, the conventional level used for RESP charge calculations.

To assign charges:

1. Read a chemical structure into ICM and convert it to a 3D ICM object.
2. Check that hydrogen atoms are present and the atomic formal charges are correct.
3. Select MolMechanics/Quantum Mechanics/Set Charges.

The fitted values are assigned as the molecule's atomic partial charges. Chemically equivalent atoms, such as the three hydrogen atoms of a methyl group, are constrained to receive identical charges.

Further information: set charge quantum and PsiRESP documentation.