Protein folding by ‘levels of separation’: A hypothesis

The protein folding process has been studied both computationally and experimentally for over 30 years. To date there is no detailed mechanism to explain the formation of long-range interactions between the transition and native states. Long-range interactions are the principle determinants of the tertiary structure. We present a theoretical model which proposes a mechanism for the acquisition of these interactions as they form in a modified version of ‘degrees of separation’, that we term ‘levels of separation’. It is based on the integration of network science and biochemistry.

► Proteins can be modeled as network systems.
► We propose that proteins fold in ‘levels of separation’.
► This hypothesis provides a mechanism for the formation of long-range interactions.
► We focus on the transition-to-native state.