# Periodicity-dependent stiffness of periodic hydrophilic-hydrophobic hetero-polymers

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## Abstract

From extensive Monte Carlo simulations of a Larson model of perfectly periodic heteropolymers (PHP) in water a striking stiffening is observed as the period of the alternating hydrophobic and hydrophilic blocks is shortened. At short period and low temperature needle-like conformations are the stable conformation. As temperature is increased thermal fluctuations induce kinks and bends. At large periods compact oligomeric globules are observed. From the generalized Larson prescription, originally developed for modelling surfactant molecules in aqueous solutions, we find that the shorter is the period the more stretched is the PHP. This novel effect is expected to stimulate polymer synthesis and trigger research on the rheology of aqueous periodic heteropolymer solutions.

PACS Nos. 82.70.-y; 87.15.Aa; 61.41.+e

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Almost all the important ”molecules of life”, e.g., DNA, RNA and proteins, are hetero-polymers. Therefore, in order to gain insight into the in-vivo ”structure” and ”function” of these macromolecules, in recent years physicists and chemists have been studying the in-vitro structure and dynamics of simpler hetero-polymers consisting of only two different types of monomers. The sequence distribution is totally random in what are known as random heteropolymers (RHP) . The RHP are of special interest to theorists also because of their close relation with the random energy model and spin glasses; these similarities and the unusual properties of the RHP are consequence of the combination of quenched disorder and a special type of frustration arising from the competing interactions in the RHP. Very recently, random heteropolymers with correlated sequence distribution has also been considered theoretically. On the other hand, perfectly periodic heteropolymers (PHP) have begun to receive attention only very recently. Orlandini and Garel carried out what may be loosely called the first in-vacuo Monte Carlo (MC) simulations of PHP. The aim of this paper is to report the results of in-vitro MC simulations of a very simple model of PHP in water to demonstrate a novel dependence of the stiffness of the PHP on the periodicity of the hydrophilic (or, hydrophobic) segments.

We follow the recent reformulation of the Larson model of surfactants in water to model the PHP in water. In the spirit of lattice gas models, the system is modelled as a simple cubic lattice of size $`L_x\times L_y\times L_z`$. Each of the molecules of water can occupy a single lattice site. A surfactant occupies several lattice sites successive pairs of which are connected by a nearest-neighbour bond of fixed length. We shall refer to each site on the surfactants as a monomer. The primary structure of each PHP can be described by the symbol $`I_pO_pI_pO_p\mathrm{}\mathrm{}I_pO_p`$ where $`I`$ and $`O`$ refer to the hydrophilic and hydrophobic monomers and the basic building block $`I_pO_p`$, each of length $`L_p`$, is repeated $`n`$ times such that $`2L_pn=L_a`$ is the total length of the PHP. No monomer is allowed to occupy a site which is already occupied by a water molecule. Besides, no two monomers of the PHP are allowed to occupy the same site simultaneously.

If the chain consisted of only hydrophilic monomers it would behave exactly as a self-avoing walk in vacuo because of the complete identity between the hydrophilic monomers and the molecules of water. On the other hand, if it consisted of only hydrophobic monomers it would collapse forming a compact globule. What makes the model PHP so interesting is the competition between these two conformations arising from the competing hydrophilic-hydrophobic effects.

For the convenience of computation, we have reformulated the model of PHP in terms of classical Ising-spin-like variables, generalizing the corresponding formulation for the single-chain surfactants . In this reformulation, a classical Ising-spin-like variable $`S`$ is assigned to each lattice site; $`S_i=1`$ if the $`i`$-th lattice site is occupied by a water molecule. If the $`j`$-th site is occupied by a monomer belonging to a PHP then $`S_j=1,1`$ depending on whether the monomer at the $`j`$th site is hydrophilic or, hydrophobic. respectively. The temperature $`T`$ of the system is measured in the units of $`J/k_B`$ where $`J`$ denotes the strength of the interaction between a spin and its six nearest-neighbours. This reformulation in terms of Ising-spin-like variables has been successfully used in studying a wide variety of phenomena exhibited by various types of surfactant molecules in aqueous media and should not be confused with magnetic polymers. Besides, molecular dynamics simulation of similar molecular models have also been carried out to study the spontaneous formation of self-assemblies of surfactant molecules.

Both the position of the center of mass and the conformation of the PHP is random in the initial state of the system. The allowed moves of the PHP are the same as those of the small surfactants in the Larson model (see ref), namely, reptation, buckling and anti-buckling (also called pull) and kink movement. Starting from the initial state, the system is allowed to evolve following the standard Metropolis algorithm: each of the attempts to move the PHP takes place certainly if $`\mathrm{\Delta }E<0`$ and with a probability proportional to $`\mathrm{exp}(\mathrm{\Delta }E/T)`$ if $`\mathrm{\Delta }E0`$, where $`\mathrm{\Delta }E`$ is the change in energy that would be caused by the proposed move of the PHP.

In order to collect informations on the qualitative features of the conformations of the PHP we have directly looked at many snapshots of the PHP at various stages of MC updating of the state of the system. We have also computed several different quantities which provide important quantitative informations on various aspects of the conformation of the PHP.

A gross measure of the ”size” of the PHP in water is given by its radius of gyration

$$R=\underset{j=1}{\overset{L_a}{}}(\stackrel{}{r}_j\stackrel{}{R}_{cm})^2$$
(1)   
where $`\stackrel{}{r}_j`$ is the position vector of the $`j`$-th monomer and $`\stackrel{}{R}_{cm}`$ is the position of the center of mass which is defined as $`R_{cm}=(1/L_a)_{j=1}^{L_a}\stackrel{}{r}_j`$.

Insight into the composition of the local neighbourhood of an arbitrary hydrophilic monomer can be gained by computing the quantities $`N_{ii},N_{io}`$ and $`N_{iw}`$ which are the average numbers of its nearest-neighbour sites that are occupied by a hydrophilic monomer, a hydrophobic monomer and a water molecule, respectively. Similarly, the composition of the local neighbourhood of an arbitrary hydrophobic monomer is reflected in the numbers $`N_{oi},N_{oo}`$ and $`N_{ow}`$, which are the average numbers of its nearest-neighbour sites that are occupied by a hydrophilic monomer, a hydrophobic monomer and a water molecule, respectively. Obviously, $`N_{io}=N_{oi}`$ as, throughout this paper, we consider PHP consisting of equal number of hydrophilic and hydrophobic segments of the same length $`L_p`$.

Suppose an index $`j`$ ($`j=1,2,\mathrm{},L_a`$) labels the monomers sequentially along the primary structure of the PHP chain from one fixed end. The $`i,j`$-th element, $`C_{ij}`$, of the contact map $`C`$ is defined to be non-zero if and only if in at least one of its equilibrium configurations the $`i`$-th and the $`j`$-th monomers (irrespective of whether hydrophilic or hydrophobic) are not nearest-neighbours along the chain but occupy two nearest-neighbour lattice sites. The contact map has been used to reconstruct the three-dimensional conformation of bio-polymers.

For a given $`L_a`$, $`L_p`$ and $`T`$, after equilibration, we have computed the above-mentioned quantities of our interest. Then we have repeated the calculations for several values of $`L_a`$, $`L_p`$ and $`T`$. All the data reported in this letter, however, have been generated for $`L_p=400`$, corresponding to the longest PHP, for which we could sample, after equilibration, sufficiently large number of configurations required for averaging.

For a fixed $`L_a=400`$, typical snapshots of the PHP for a few different $`L_p`$ are shown in the figs.1a-d. The PHP is very stiff for $`L_p=4`$ (fig.1a). For intermediate values of $`L_p`$, e.g., $`L_p=40`$ (fig.1b) and $`L_p=50`$ (fig.1c), it has a necklace-like conformation where ”beads” of hydrophobic monomers are connected by hydrophilic chains. Finally, when $`L_p`$ is of the same order as $`L_a`$, e.g., $`L_p=100`$ (fig.1d), the hydrophic monomers form a large collapsed globule surrounded by hydrophobic monomers.

Each of the hydrophilic (hydrophobic) monomers has a tendency to have hydrophilic (hydrophobic) nearest-neighbours and avoid having hydrophobic (hydrophilic) nearest-neighbours. The snapshots shown in fig.1 also indicate that a longer $`L_p`$ enables the PHP to satisfy these tendencies. This can be shown more quantitatively (fig.2) by plotting $`N_{ii}`$, $`N_{io},N_{iw},N_{oo}`$ and $`N_{ow}`$ against $`f=L_p/L_a`$ at a fixed temperature $`T=2.0`$.

One striking feature of the PHP is that the shorter is the period the more stretched is the PHP, as shown by the snapshots in fig.1. This trend of variation is reflected in the structure of the contact maps, shown in the figs.3a-d, corresponding to the figs.1a-d, respectively. In the contact map for $`f=L_p/L_a=0.01`$ there are very few non-zero elements outside the diagonal backbone of the map. With increase of $`f`$ more and more non-zero elements far from the diagonal backbone appear signalling folding or collapse of the PHP. This trend of variation of the ”size” of the PHP can be seen quantitatively also in fig.4 where we plot the radius of gyration $`R`$ of the PHP as a function of $`f`$.

Finally, keeping $`f`$ fixed at a small value, say $`f=0.01`$, corresponding to which the PHP is very stiff, if we raise $`T`$, the $`R`$ of the PHP falls monotonically with increasing $`T`$ (fig.5), as expected, because of stronger thermal fluctuations.

In summary, in this letter we have developed a Larson-type model of a periodic hetero-polymer. By carrying out MC simulations of these model PHP, each consisting of equal numbers of hydrophilic and hydrophobic monomers, we have investigated the effects of varying the period on its conformations in equilibrium. We have observed that, at a given temperature, the smaller is the ratio $`f=L_p/L_a`$, the stiffer is the PHP. We would like to emphasize that the stiffness of the PHP at a fixed temperature decreases with increasing $`L_p=L_a/(2n)`$, where $`n`$ is the number of segments of each type, in spite of the fact that, $`nL_p`$, the total number of hydrophobic monomers remains fixed for the given $`L_a`$. This prediction, we believe, can be tested directly in laboratory experiments.

We thank E. Domany for enlightening discussions on contact maps and L. Santen for help with the graphics. This work is supported by the SFB341 Köln-Aachen-Jülich and German-Israeli Foundation.

$``$ On leave from the Physics Department, I.I.T., Kanpur 208016, India.