Insights from Coarse-Grained Gō Models for Protein Folding and Dynamics

Abstract

Exploring the landscape of large scale conformational changes such as protein folding at atomistic detail poses a considerable computational challenge. Coarse-grained representations of the peptide chain have therefore been developed and over the last decade have proved extremely valuable. These include topology-based Gō models, which constitute a smooth and funnel-like approximation to the folding landscape. We review the many variations of the Gō model that have been employed to yield insight into folding mechanisms. Their success has been interpreted as a consequence of the dominant role of the native topology in folding. The role of local contact density in determining protein dynamics is also discussed and is used to explain the ability of Gō-like models to capture sequence effects in folding and elucidate conformational transitions.

Is there an en route folding intermediate for cold shock proteins?

“…Despite the simplicity and wellknown unphysical aspects, Go-like models have been used, with some success, to study folding dynamics 35,[37][38][39][40][41][42]44,45 and predict folding rates 46 as it is widely assumed that the folding mechanism is mainly determined by a protein's native structure. 40,44,47 Generally, Go models provide a good description of the energy landscape of the folded state, the TS, and the nativelike intermediates. 40,44,[47][48][49] It is possible to extract meaningful results about the folding mechanism and the TS for those small proteins which directly collapse to a native-like TS.…”

“…Other than physical and empirical force fields, structure-centric Go-like models have been widely used to study protein folding mechanisms, [35][36][37][38][39][40][41][42][43][44][45] especially when there are no other suitable force fields available. Despite the simplicity and wellknown unphysical aspects, Go-like models have been used, with some success, to study folding dynamics 35,[37][38][39][40][41][42]44,45 and predict folding rates 46 as it is widely assumed that the folding mechanism is mainly determined by a protein's native structure. 40,44,47 Generally, Go models provide a good description of the energy landscape of the folded state, the TS, and the nativelike intermediates.…”

“…40,44,47 Generally, Go models provide a good description of the energy landscape of the folded state, the TS, and the nativelike intermediates. 40,44,[47][48][49] It is possible to extract meaningful results about the folding mechanism and the TS for those small proteins which directly collapse to a native-like TS. Go models are known to have limitation of describing non-native-like collapsed structures, for example, those misfolded structures, and the contributions from non-native interactions.…”

Modulation of frustration in folding by sequence permutation

“…Another perspective is provided by the branched chain aliphatic side chains (BASiC) hypothesis, which supposes that large clusters of isoleucine, leucine, and valine (ILV) side chains serve as cores of stability in folding intermediates (11,14). Both these clusters have been shown to have a high contact density (22). CheY has two ILV clusters, each serving to fuse the surface helices to each other and to the central β-sheet (Fig.…”

Coarse-grained simulations for organic molecular liquids based on Gay-Berne and electric multipole potentials

“…Therefore, a variety of CG models [21][22][23][24][25][26][27][28] have emerged to overcome the obstacle. Nowadays, different coarse-graining strategies [29,30] have been adopted with a reasonable balance between accuracy and efficiency for different purposes or different applications, enabling one to simulate much longer time scales and larger systems to learn the interesting phenomena that are inaccessible to all-atom models.…”