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Energy landscape theory describes how a full-length protein can attain its native fold after sampling only a tiny fraction of all possible structures. Although protein folding is now understood to be concomitant with synthesis on the ribosome there have been few attempts to modify energy landscape theory by accounting for cotranslational folding. This paper introduces a model for cotranslational folding that leads to a natural definition of a nested energy landscape. By applying concepts drawn from submanifold differential geometry the dynamics of protein folding on the ribosome can be explored in a quantitative manner and conditions on the nested potential energy landscapes for a good cotranslational folder are obtained. A generalisation of diffusion rate theory using van Kampens technique of composite stochastic processes is then used to account for entropic contributions and the effects of variable translation rates on cotranslational folding. This stochastic approach agrees well with experimental results and Hamiltionian formalism in the deterministic limit.
The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, an
The intricate three-dimensional geometries of protein tertiary structures underlie protein function and emerge through a folding process from one-dimensional chains of amino acids. The exact spatial sequence and configuration of amino acids, the bioc
We report the folding thermodynamics of ccUUCGgg and ccGAGAgg RNA tetraloops using atomistic molecular dynamics simulations. We obtain a previously unreported estimation of the folding free energy using parallel tempering in combination with well-tem
Significant progress in computer hardware and software have enabled molecular dynamics (MD) simulations to model complex biological phenomena such as protein folding. However, enabling MD simulations to access biologically relevant timescales (e.g.,
Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins. In comparis