TY - JOUR
T1 - Exploring biomolecular energy landscapes
AU - Joseph, Jerelle A.
AU - Röder, Konstantin
AU - Chakraborty, Debayan
AU - Mantell, Rosemary G.
AU - Wales, David J.
N1 - Funding Information:
This work was supported by the Engineering and Physical Sciences Research Council (RGM and KR), the Cambridge Commonwealth, European and International Trust (DC), and the Gates Cambridge Trust (JAJ).
Publisher Copyright:
© 2017 The Royal Society of Chemistry.
PY - 2017
Y1 - 2017
N2 - The potential energy landscape perspective provides both a conceptual and a computational framework for predicting, understanding and designing molecular properties. In this Feature Article, we highlight some recent advances that greatly facilitate structure prediction and analysis of global thermodynamics and kinetics in proteins and nucleic acids. The geometry optimisation procedures, on which these calculations are based, can be accelerated significantly using local rigidification of selected degrees of freedom, and through implementations on graphics processing units. Results of progressive local rigidification are first summarised for trpzip1, including a systematic analysis of the heat capacity and rearrangement rates. Benchmarks for all the essential optimisation procedures are then provided for a variety of proteins. Applications are then illustrated from a study of how mutation affects the energy landscape for a coiled-coil protein, and for transitions in helix morphology for a DNA duplex. Both systems exhibit an intrinsically multifunnel landscape, with the potential to act as biomolecular switches.
AB - The potential energy landscape perspective provides both a conceptual and a computational framework for predicting, understanding and designing molecular properties. In this Feature Article, we highlight some recent advances that greatly facilitate structure prediction and analysis of global thermodynamics and kinetics in proteins and nucleic acids. The geometry optimisation procedures, on which these calculations are based, can be accelerated significantly using local rigidification of selected degrees of freedom, and through implementations on graphics processing units. Results of progressive local rigidification are first summarised for trpzip1, including a systematic analysis of the heat capacity and rearrangement rates. Benchmarks for all the essential optimisation procedures are then provided for a variety of proteins. Applications are then illustrated from a study of how mutation affects the energy landscape for a coiled-coil protein, and for transitions in helix morphology for a DNA duplex. Both systems exhibit an intrinsically multifunnel landscape, with the potential to act as biomolecular switches.
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U2 - 10.1039/c7cc02413d
DO - 10.1039/c7cc02413d
M3 - Review article
C2 - 28489083
AN - SCOPUS:85021752277
SN - 1359-7345
VL - 53
SP - 6974
EP - 6988
JO - Chemical Communications
JF - Chemical Communications
IS - 52
ER -