Affiliation:
1. Department of Chemistry Durham University Stockton Road Durham DH1 3LE UK
2. Previous affiliation: Yusuf Hamied Department of Chemistry University of Cambridge Lensfield Road Cambridge CB2 1EW UK
3. Randall Centre for Cell & Molecular Biophysics King's College London Guy's Campus, Great Maze Pond London SE1 1UL UK
Abstract
AbstractChameleon sequences are amino acid sequences found in several distinct configurations in experiment. They challenge our understanding of the link between sequence and structure, and provide insight into structural competition in proteins. Here, we study the energy landscapes for three such sequences, and interrogate how pulling and twisting forces impact the available structural ensembles. Chameleon sequences do not necessarily exhibit multiple structural ensembles on a multifunnel energy landscape when we consider them in isolation. The application of even small forces leads to drastic changes in the energy landscapes. For pulling forces, we observe transitions from helical to extended structures in a very small span of forces. For twisting forces, the picture is much more complex, and highly dependent on the magnitude and handedness of the applied force as well as the reference angle for the twist. Depending on these parameters, more complex and more simplistic energy landscapes are observed alongside more and less diverse structural ensembles. The impact of even small forces is significant, confirming their likely role in folding events. In addition, small forces exerted by the remaining scaffold of a protein may be sufficient to lead to the adoption of a specific structural ensemble by a chameleon sequence.
Funder
Cambridge Philosophical Society
Subject
Physical and Theoretical Chemistry,Atomic and Molecular Physics, and Optics