Topology to geometry in protein folding: beta-lactoglobulin

ARIEL FERNANDEZ; ANDRES COLUBRI; R. STEPHEN BERRY

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2000 vol. 97 p. 14062 - 14066

0027-8424

Evolution of protein structure from random coil to native is first represented topologically by its time-dependent sequences of discretized Ramachandran basins occupied by successive backbone residues. Introducing energetic and entropic criteria at each instant of observation transforms the description from a structurally ambiguous topological representation to an unambiguous geometric picture of the folding process. The method is applied with success to folding of beta-lactoglobulin, traditionally perplexing be- cause of its reputed nonhierarchical folding pattern. This molecule passes through a stage of transient, flickering helical structure, until a bit of tertiary structure forms that stabilizes the system long enough to allow it to pass to its native beta-sheet.