Conformational transitions of heteropolymers in dilute solutions

In this paper we extend the Gaussian self-consistent method to permit study of the equilibrium and kinetics of conformational transitions for heteropolymers with any given primary sequence. The kinetic equations earlier derived by us are transformed to a form containing only the mean squared distances between pairs of monomers. These equations are further expressed in terms of instantaneous gradients of the variational free energy. The method allowed us to study exhaustively the stability and conformational structure of some periodic and random aperiodic sequences. A typical phase diagram of a fairly long amphiphilic heteropolymer chain is found to contain phases of the extended coil, the homogeneous globule, the micro-phase separated globule, and a large number of frustrated states, which result in conformational phases of the random coil and the frozen globule. We have also found that for a certain class of sequences the frustrated phases are suppressed. The kinetics of folding from the extended coil to the globule proceeds through non-equilibrium states possessing locally compacted, but partially misfolded and frustrated, structure. This results in a rather complicated multistep kinetic process typical of glassy systems.Comment: 15 pages, RevTeX, 20 ps figures, accepted for publication in Phys. Rev.

Mechanical response of random heteropolymers

We present an analytical theory for heteropolymer deformation, as exemplified experimentally by stretching of single protein molecules. Using a mean-field replica theory, we determine phase diagrams for stress-induced unfolding of typical random sequences. This transition is sharp in the limit of infinitely long chain molecules. But for chain lengths relevant to biological macromolecules, partially unfolded conformations prevail over an intermediate range of stress. These necklace-like structures, comprised of alternating compact and extended subunits, are stabilized by quenched variations in the composition of finite chain segments. The most stable arrangements of these subunits are largely determined by preferential extension of segments rich in solvophilic monomers. This predicted significance of necklace structures explains recent observations in protein stretching experiments. We examine the statistical features of select sequences that give rise to mechanical strength and may thus have guided the evolution of proteins that carry out mechanical functions in living cells.Comment: 10 pages, 6 figure

Glassy phases in Random Heteropolymers with correlated sequences

We develop a new analytic approach for the study of lattice heteropolymers, and apply it to copolymers with correlated Markovian sequences. According to our analysis, heteropolymers present three different dense phases depending upon the temperature, the nature of the monomer interactions, and the sequence correlations: (i) a liquid phase, (ii) a ``soft glass'' phase, and (iii) a ``frozen glass'' phase. The presence of the new intermediate ``soft glass'' phase is predicted for instance in the case of polyampholytes with sequences that favor the alternation of monomers. Our approach is based on the cavity method, a refined Bethe Peierls approximation adapted to frustrated systems. It amounts to a mean field treatment in which the nearest neighbor correlations, which are crucial in the dense phases of heteropolymers, are handled exactly. This approach is powerful and versatile, it can be improved systematically and generalized to other polymeric systems

The Phase Diagram of Random Heteropolymers

We propose a new analytic approach to study the phase diagram of random heteropolymers, based on the cavity method. For copolymers we analyze the nature and phenomenology of the glass transition as a function of sequence correlations. Depending on these correlations, we find that two different scenarios for the glass transition can occur. We show that, beside the much studied possibility of an abrupt freezing transition at low temperature, the system can exhibit, upon cooling, a first transition to a soft glass phase with fully broken replica symmetry and a continuously growing degree of freezing as the temperature is lowered.Comment: 4 pages, 3 figures; published versio

Polymer adsorption onto random planar surfaces: Interplay of polymer and surface correlation

We study the adsorption of homogeneous or heterogeneous polymers onto heterogeneous planar surfaces with exponentially decaying site-site correlations, using a variational reference system approach. As a main result, we derive simple equations for the adsorption-desorption transition line. We show that the adsorption threshold is the same for systems with quenched and annealed disorder. The results are discussed with respect to their implications for the physics of molecular recognition

Reversible stretching of homopolymers and random heteropolymers

We have analyzed the equilibrium response of chain molecules to stretching. For a homogeneous sequence of monomers, the induced transition from compact globule to extended coil below the $\theta$-temperature is predicted to be sharp. For random sequences, however, the transition may be smoothed by a prevalence of necklace-like structures, in which globular regions and coil regions coexist in a single chain. As we show in the context of a random copolymer, preferential solvation of one monomer type lends stability to such structures. The range of stretching forces over which necklaces are stable is sensitive to chain length as well as sequence statistics.Comment: 14 pages, 4 figure

Dynamics of heteropolymers in dilute solution: effective equation of motion and relaxation spectrum

The dynamics of a heteropolymer chain in solution is studied in the limit of long chain length. Using functional integral representation we derive an effective equation of motion, in which the heterogeneity of the chain manifests itself as a time-dependent excluded volume effect. At the mean field level, the heteropolymer chain is therefore dynamically equivalent to a homopolymer chain with both time-independent and time-dependent excluded volume effects. The perturbed relaxation spectrum is also calculated. We find that heterogeneity also renormalizes the relaxation spectrum. However, we find, to the lowest order in heterogeneity, that the relaxation spectrum does not exhibit any dynamic freezing, at the point when static (equilibrium) ``freezing'' transition occurs in heteropolymer. Namely, the breaking of fluctuation-dissipation theorem (FDT) proposed for spin glass dynamics does not have dynamic effect in heteropolymer, as far as relaxation spectrum is concerned. The implication of this result is discussed

Multicanonical Study of Coarse-Grained Off-Lattice Models for Folding Heteropolymers

We have performed multicanonical simulations of hydrophobic-hydrophilic heteropolymers with two simple effective, coarse-grained off-lattice models to study the influence of specific interactions in the models on conformational transitions of selected sequences with 20 monomers. Another aspect of the investigation was the comparison with the purely hydrophobic homopolymer and the study of general conformational properties induced by the "disorder" in the sequence of a heteropolymer. Furthermore, we applied an optimization algorithm to sequences with up to 55 monomers and compared the global-energy minimum found with lowest-energy states identified within the multicanonical simulation. This was used to find out how reliable the multicanonical method samples the free-energy landscape, in particular for low temperatures.Comment: 11 pages, RevTeX, 10 Postscript figures, Author Information under http://www.physik.uni-leipzig.de/index.php?id=2

From Collapse to Freezing in Random Heteropolymers

We consider a two-letter self-avoiding (square) lattice heteropolymer model of N_H (out ofN) attracting sites. At zero temperature, permanent links are formed leading to collapse structures for any fraction rho_H=N_H/N. The average chain size scales as R = N^{1/d}F(rho_H) (d is space dimension). As rho_H --> 0, F(rho_H) ~ rho_H^z with z={1/d-nu}=-1/4 for d=2. Moreover, for 0 < rho_H < 1, entropy approaches zero as N --> infty (being finite for a homopolymer). An abrupt decrease in entropy occurs at the phase boundary between the swollen (R ~ N^nu) and collapsed region. Scaling arguments predict different regimes depending on the ensemble of crosslinks. Some implications to the protein folding problem are discussed.Comment: 4 pages, Revtex, figs upon request. New interpretation and emphasis. Submitted to Europhys.Let

What thermodynamic features characterize good and bad folders? Results from a simplified off-lattice protein model

The thermodynamics of the small SH3 protein domain is studied by means of a simplified model where each bead-like amino acid interacts with the others through a contact potential controlled by a 20x20 random matrix. Good folding sequences, characterized by a low native energy, display three main thermodynamical phases, namely a coil-like phase, an unfolded globule and a folded phase (plus other two phases, namely frozen and random coil, populated only at extremes temperatures). Interestingly, the unfolded globule has some regions already structured. Poorly designed sequences, on the other hand, display a wide transition from the random coil to a frozen state. The comparison with the analytic theory of heteropolymers is discussed