The Complexity and Fuzziness of Conformational Chemistry: Theory and Applications

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.

Authors

Institutions

Publication Details

Journal
Molecules
Published
2026-10-28
DOI
https://doi.org/10.3390/molecules31213886
Primary Topic
Protein Structure and Dynamics
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

The Complexity and Fuzziness of Conformational Chemistry: Theory and Applications

Pier Luigi Gentili, Vladimir Nikolaevich Uversky
Molecules
Protein Structure and Dynamics
article

The Complexity and Fuzziness of Conformational Chemistry: Theory and Applications

Pier Luigi Gentili, Vladimir Nikolaevich Uversky
article en

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.

MoleculesVol. 31(21)
University of Perugia (IT), USF Health Byrd Alzheimer's Institute (US)
Università degli Studi di Perugia
Openalex Percentile: Top 22%
Protein Structure and Dynamics
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.

Laika access coming soon