The Complexity and Fuzziness of Conformational Chemistry: Theory and Applications
- 1Department of Chemistry, Biology, and Biotechnology, Università Degli Studi di Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
- 2Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
Abstract
Molecular structure is traditionally described in terms of chemical composition, atomic connectivity, and three-dimensional geometry. However, many molecules, particularly biomacromolecules, exist not as single structures but as dynamic ensembles of interconverting conformers whose populations depend on the surrounding physicochemical context. This work proposes that such conformational ensembles can be interpreted as molecular fuzzy sets, thereby establishing a conceptual bridge between conformational chemistry, information theory, and fuzzy logic. The theoretical framework is introduced by representing molecular structures as adjacency matrices and extending this description to conformational distributions. Experimental evidence is discussed through the photochromic behavior of merocyanines, whose temperature- and environment-dependent conformational distributions encode measurable amounts of fuzzy information. Further support is provided by proteins, DNA, and RNA, where conformational heterogeneity underlies multifunctionality, gene regulation, alternative splicing, molecular recognition, and adaptive cellular responses. Within this perspective, biological function emerges from context-dependent distributions of molecular states rather than from unique static structures. Conformational ensembles are also described as thermalized quantum mixed states, suggesting new links between molecular complexity, fuzzy information processing, and quantum biological phenomena. Finally, the implications of molecular fuzziness for Chemical Artificial Intelligence are discussed, highlighting the possibility of exploiting molecular conformational dynamics as a substrate for adaptive, context-sensitive, and chemically embodied information processing.
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BibTeX
@article{gentili2026complexity,
title = {{The Complexity and Fuzziness of Conformational Chemistry: Theory and Applications}},
author = {Pier Luigi Gentili and Vladimir N. Uversky},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31213886},
url = {https://www.mdpi.com/1420-3049/31/21/3886},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Complexity and Fuzziness of Conformational Chemistry: Theory and Applications
AU - Pier Luigi Gentili
AU - Vladimir N. Uversky
PY - 2026
DA - 2026/10/28
JO - Molecules
DO - 10.3390/molecules31213886
UR - https://www.mdpi.com/1420-3049/31/21/3886
AB - Molecular structure is traditionally described in terms of chemical composition, atomic connectivity, and three-dimensional geometry. However, many molecules, particularly biomacromolecules, exist not as single structures but as dynamic ensembles of interconverting conformers whose populations depend on the surrounding physicochemical context. This work proposes that such conformational ensembles can be interpreted as molecular fuzzy sets, thereby establishing a conceptual bridge between conformational chemistry, information theory, and fuzzy logic. The theoretical framework is introduced by representing molecular structures as adjacency matrices and extending this description to conformational distributions. Experimental evidence is discussed through the photochromic behavior of merocyanines, whose temperature- and environment-dependent conformational distributions encode measurable amounts of fuzzy information. Further support is provided by proteins, DNA, and RNA, where conformational heterogeneity underlies multifunctionality, gene regulation, alternative splicing, molecular recognition, and adaptive cellular responses. Within this perspective, biological function emerges from context-dependent distributions of molecular states rather than from unique static structures. Conformational ensembles are also described as thermalized quantum mixed states, suggesting new links between molecular complexity, fuzzy information processing, and quantum biological phenomena. Finally, the implications of molecular fuzziness for Chemical Artificial Intelligence are discussed, highlighting the possibility of exploiting molecular conformational dynamics as a substrate for adaptive, context-sensitive, and chemically embodied information processing.
SN - 1420-3049
ER -