Designability, thermodynamic stability, and dynamics in protein folding: a lattice model study

Abstract

In the framework of a lattice-model study of protein folding, we investigate the interplay between designability, thermodynamic stability, and kinetics. To be ``protein-like'', heteropolymers must be thermodynamically stable, stable against mutating the amino-acid sequence, and must be fast folders. We find two criteria which, together, guarantee that a sequence will be ``protein like'': i) the ground state is a highly designable stucture, i. e. the native structure is the ground state of a large number of sequences, and ii) the sequence has a large $\Delta /\Gamma$ ratio, $\Delta$ being the average energy separation between the ground state and the excited compact conformations, and $\Gamma$ the dispersion in energy of excited compact conformations. These two criteria are not incompatible since, on average, sequences whose ground states are highly designable structures have large $\Delta /\Gamma$ values. These two criteria require knowledge only of the compact-state spectrum. These claims are substantiated by the study of 45 sequences, with various values of $\Delta /\Gamma$ and various degrees of designability, by means of a Borst-Kalos-Lebowitz algorithm, and the Ferrenberg-Swendsen histogram optimization method. Finally, we report on the reasons for slow folding. A comparison between a very slow folding sequence, an average folding one and a fast folding one suggests that slow folding originates from a proliferation of nearly compact low-energy conformations, not present for fast folders.

24 pages, 10 figures, 2 tables

References in corpus (6)

• Why Do Proteins Look Like Proteins?
• Folding Kinetics of Protein Like Heteropolymers
• Nature of Driving Force for Protein Folding -- A Result From Analyzing the Statistical Potential
• Kinetic and thermodynamic analysis of proteinlike heteropolymers: Monte Carlo histogram technique
• Are Protein Folds Atypical?
• Stability Threshold as a Selection Principle for Protein Design

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• Simple Models of the Protein Folding Problem
• Fast Tree Search for Enumeration of a Lattice Model of Protein Folding
• Protein folding dynamics via quantification of kinematic energy landscape
• Geometry Selects Highly Designable Structures
• Protein folding rates correlate with heterogeneity of folding mechanism
• Protein Ground State Candidates in a Simple Model: An Exact Enumeration
• Statistical mechanics of RNA folding: importance of alphabet size
• Design of Toy Proteins Capable to Rearrange Conformations in a Mechanical Fashion
• Glassy Dynamics of Protein Folding
• Structure Space of Model Proteins --A Principle Component Analysis
• HP-sequence design for lattice proteins - an exact enumeration study on diamond as well as square lattice
• The Origin of the Designability of Protein Structures
• Note on irreducible approach to reducible second-class constraints
• Conformation-networks of two-dimensional lattice homopolymers
• Unfolding designable structures