Repository Description

This repository contains the complete conformer-generation, quantum-chemical evaluation, and comparative analysis workflow as used in this study. It provides all input structures, scripts, calculation outputs, and post-processing tools required to reproduce the conformational sampling, clustering, energetic ranking, and Boltzmann population analysis.

The archive is organized in a fully reproducible, folder-based structure that reflects the hierarchical workflow:

1. Conformer generation (Open Babel Confab)
   A systematic scan over energy cutoff (Ecut) and RMSD cutoff parameters was performed to identify stable conformational families. The six-conformer regime selected for detailed study is documented and reproducible from the included scripts.

2. Quantum-chemical calculations (TeraChem)
   For the six selected conformers, the repository contains:

   • Single-point electronic structure calculations (QC_Escf)

   • Geometry optimizations at two levels:

     • RevPBE0 / LANL2DZ-ECP + COSMO + D3 (basic optimization)

     • RevPBE0 / Ahlrichs pVDZ + COSMO + D3 (refined optimization)

   Optimizations were carried out using multiple minimizer and coordinate combinations (Cartesian, TRIC, new minimizer, DLF minimizer) to ensure robust convergence.

3. Force-field reference calculations
   Open Babel force-field single-point energies are provided for direct comparison with quantum-chemical results.

4. Method-independent graphical analysis
   A unified analysis toolkit (Graphical_analysis) is included and used consistently for:

   • RMSD matrix construction

   • Hierarchical clustering

   • Conformer family assignment

   • Relative energy evaluation

   • Boltzmann population analysis

   • Generation of dendrograms, heatmaps, and energy distribution plots

   The same scripts are applied to:

   • Force-field energies

   • QC single-point results

   • Optimized QC geometries

   This guarantees methodological consistency across all comparisons.

Scientific Scope

The repository enables systematic investigation of:

• The sensitivity of conformer identification to RMSD and energy cutoffs

• Stability of conformational families under geometry optimization

• Energy reordering upon relaxation

• Agreement between force-field and quantum-chemical rankings

• Statistical conformer populations based on Boltzmann weighting

The structure of the archive ensures that all reported figures and tables can be regenerated from the included raw outputs and scripts.

Reproducibility

All analysis steps are transparent and reproducible:

• Raw conformer ensembles are included.

• All TeraChem input (qcconfig) and output files are provided.

• Post-processing scripts for RMSD calculation and clustering are included.

• Final CSV tables and PDF figures are archived.