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Protein dynamics, folding and misfolding: from basic physical chemistry to human conformational diseases
Author(s) -
Ferreira Sérgio T,
De Felice Fernanda G
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02491-7
Subject(s) - chemistry , protein folding , folding (dsp implementation) , molecular dynamics , protein subunit , biophysics , dissociation (chemistry) , conformational isomerism , population , protein structure , conformational ensembles , prion protein , molecule , biochemistry , computational chemistry , biology , medicine , disease , pathology , demography , organic chemistry , sociology , electrical engineering , gene , engineering
Proteins exhibit a variety of motions ranging from amino acid side‐chain rotations to the motions of large domains. Recognition of their conformational flexibility has led to the view that protein molecules undergo fast dynamic interconversion between different conformational substates. This proposal has received support from a wide variety of experimental techniques and from computer simulations of protein dynamics. More recently, studies of the subunit dissociation of oligomeric proteins induced by hydrostatic pressure have shown that the characteristic times for subunit exchange between oligomers and for interconversion between different conformations may be rather slow (hours or days). In such cases, proteins cannot be treated as an ensemble of rapidly interconverting conformational substates, but rather as a persistently heterogeneous population of different long‐lived conformers. This is reminiscent of the deterministic behavior exhibited by macroscopic bodies, and may have important implications for our understanding of protein folding and biological functions. Here, we propose that the deterministic behavior of proteins may be closely related to the genesis of conformational diseases, a class of pathological conditions that includes transmissible spongiform encephalopathies, Alzheimer's disease and other amyloidosis.