Energy Landscape of the Designed Protein Top7.
|Title||Energy Landscape of the Designed Protein Top7.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Neelamraju S, Gosavi S, Wales DJ|
|Journal||J Phys Chem B|
|Date Published||2018 Nov 29|
To fold on biologically relevant timescales, proteins have evolved funnelled energy landscapes with minimal energetic trapping. However, the polymeric nature of proteins and the spatial arrangement of secondary structural elements can create topological traps and slow folding. It is challenging to identify, visualise and quantify such topological trapping. Designed proteins have not had the benefit of evolution and it has been hypothesised that de novo designed protein topologies may therefore feature more topological trapping. Structure-based models (SBMs) are inherently funnelled and remove most energetic trapping and can thus be used to isolate the effect of protein topology on the folding energy landscape. Here, we compare properties of the potential energy landscapes (PEL) of Top7, a designed protein with a topology unknown in nature, with those of S6, a naturally occurring ribosomal protein of similar size and topology. Possible kinetic traps and the energetic barriers separating them from the native state are elucidated. We find that even with an SBM, the PEL of the designed protein is more frustrated than that of the natural protein. We then quantify the effect of adding non-native hydrophobic interactions and coarse-grained side-chains through a frustration density parameter. A clear increase in frustration is observed on including side-chains, whereas adding hydrophobic interactions leads to a narrowing of the funnel and a decrease in complexity. The most likely (un)folding routes for all models are derived through the construction of "probability contact maps". The ability to quantitatively understand and optimise the organisation of the PEL for designed proteins may enable us to sculpt structure-seeking landscapes, mimicking the effect of evolution.
|Alternate Journal||J Phys Chem B|