Designing refoldable model molecules

Abstract

We report a numerical study of the design of lattice heteropolymers that can refold when the properties of only a few monomers are changed. If we assume that the effect of an external agent on a heteropolymer is to alter the interactions between its constituent monomers, our simulations provide a description of a simple allosteric transition. We characterize the free energy surfaces of the initial and the modified chain molecule. We find that there is a region of conformation space where molecules can be made to refold with minimal free energy cost. This region is accessible by thermal fluctuations. The efficiency of a motor based on such an allosteric transition would be enhanced by ''borrowing'' heat from the environment in the initial stages of the refolding, and ''paying back'' later. In fact, the power cycle of many real molecular motors does involve such a borrowing activation step.

Virtual‐Move Parallel Tempering

“…We refer to this scheme as APT (adaptive parallel tempering). [10,11] In the conventional MCMC method all information about rejected trial moves is discarded. Recently one of us proposed a scheme that makes it possible to include the contributions of rejected configurations in the sampling of averages.…”

“…For the same system we had already explored the use of the conventional APT scheme. [10] Specifically, the model protein that we consider represents a heteropolymer containing 80 amino acids, while the substrate has a fixed-space arrangement and contains 40 residues (see Figure 1). The configurational energy of the system is defined as Equation (10):…”

“…The design scheme is the same as that used in ref. [10]. In this scheme, trial mutations are accepted if the Monte Carlo acceptance criterion is satisfied for both configurations.…”

Constrained versus unconstrained folding free-energy landscapes

“…While the validity of MFP has been confirmed for lattice heteropolymers [3][4][5][6][7][8][9][10], in more realistic protein representations, a residual frustration is often observed, which prevents the systematic prediction of the native structure of natural sequences. Following the MFP, many studies have shown a strong correlation between the topology of the native structure and the folding dynamics.…”

“…Our aim is to compare, within the framework of our model, the folding of these 15 proteins in the scenarios where the interactions between the residues are either natural, optimised through a sequence design or imposed by the native structure with a Go-like potential. Several methods have been proposed to design the sequence of proteins, such that they fold into a specific target conformation [7,[46][47][48], but in this work we are going to use a method recently introduced by Coluzza [39,40], which was proven capable of producing realistic protein sequences for the Caterpillar model. For the constrained simulations, instead we replaced the residue-residue interactions of the Caterpillar model with a structure-based potential taken from the elastic network model [12,13].…”