Multiobjective exploration of intramolecular torsional space

We present an exploration-first strategy for intramolecular conformational search. Because practical quantum-chemical (QC) models are approximate, candidate retention combines energy and interaction descriptors as separate objectives, while structural diversity is preserved until post-search reduction. The SEEKER (Structural Ensemble Exploration through Knowledge-Guided Evaluation and Routing) program explores explicitly declared acyclic torsions through unit-quaternion rotations while retaining fixed ring families. We assess reference-set coverage for amino acids, the sugars D-glucose, erythrulose, and fructose, and thiopronine using per-reference nearest-candidate heavy-atom root-mean-square deviation (RMSD), minimized over graph automorphisms. Four amino-acid systems are also examined across four production seeds using same-level optimized references and candidates, all-atom RMSDs, and one-to-one assignment. Fixed-budget audits probe seed sensitivity for glycine and thiopronine, with three and six torsions, respectively. The results establish feasibility within the tested systems and motivate evaluation on larger torsional spaces and against established protocols.