For decades, scientists have understood proteins primarily through two defining features: their amino acid sequence and their three-dimensional structure. This framework has driven major advances in biology, biotechnology and medicine, culminating in recent artificial intelligence tools capable of predicting protein structures with remarkable accuracy.

Yet a fundamental challenge remains: Even when a protein’s sequence and structure are known, predicting its function, interactions and behavior often remains difficult. An international team of researchers from Japan, Finland, Italy and the United States now reports evidence that part of this missing information may lie in an often-overlooked component of proteins: the highly organized water surrounding them.

In a study published in Nature Communications, the team provides the first direct three-dimensional visualization of sequence-dependent hydration architectures surrounding peptide assemblies at subnanometer resolution using advanced three-dimensional atomic force microscopy (3D-AFM).