Abstract
The energy landscape perspective is outlined with particular reference to biomolecules that perform multiple functions. We associate these multifunctional molecules with multifunnel energy landscapes, illustrated by some selected examples, where understanding the organisation of the landscape has provided new insight into function. Conformational selection and induced fit may provide alternative routes to realisation of multifunctionality, exploiting the possibility of environmental control and distinct binding modes.
Highlights
Since the first work on protein folding over 50 years ago (Levinthal, 1966; Levinthal, 1968; Anfinsen, 1972; Anfinsen, 1973), the advance of new experimental and computational techniques has led to a greatly improved understanding of proteins and nucleic acids
This improved understanding has enabled the design of new functional biomolecules [for example (Dou et al 2018), facilitated by the emergence of design principles based on the fundamental principles governing protein folding (Huang et al, 2016; Baker, 2019)
Our exploration of potential energy landscapes is based on geometry optimisation techniques, and we extract observable thermodynamic and kinetic properties using standard tools of statistical mechanics and unimolecular rate theory (Forst, 1973; Laidler, 1987)
Summary
Since the first work on protein folding over 50 years ago (Levinthal, 1966; Levinthal, 1968; Anfinsen, 1972; Anfinsen, 1973), the advance of new experimental and computational techniques has led to a greatly improved understanding of proteins and nucleic acids. Has this research provided a better understanding of the folding process (Karplus, 2011; Wolynes et al, 2012; Wolynes, 2015), but the importance of folding and misfolding in disease has been analysed (Chiti and Dobson, 2017) This improved understanding has enabled the design of new functional biomolecules [for example (Dou et al 2018), facilitated by the emergence of design principles based on the fundamental principles governing protein folding (Huang et al, 2016; Baker, 2019). Differences in environmental conditions, as well as non-equilibrium effects due to the long timescales associated with biomolecular motions impact both experiment and simulation (Wales and Salamon, 2014) Do these effects combine to provide challenges in understanding molecular biological assemblies and their functionality, but they complicate the design and development of de novo biomolecules. We highlight recent analysis of multifunnel biomolecular energy landscapes including intrinsically disordered proteins
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