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PHYSICAL REVIEW E, VOLUME 65, 051901 Le Impact of regulatory proteins on the nonlinear dynamics of DNA M. V, Satarié! and J. A. Tuseyiiski "Facuity of Technical Sciences, 21000 Novi Sad, Serb, Yugoslavia *Depariment of Physics, Universty of Alberta, Edmonton, Canada T6G 247 (Reczived 20 November 2001; published 29 April 2002) In this paper we examine the nonlinear dynamics of a DNA chain whose exciton modes are affected by regulatory proteins that may become bound to the DNA chain by hydrogen bonds. The dynamics of the DNA. chain is described by the Peyrard-Bishop model, Since ths model gives rise to largeanplitude broad oscilla. tions of base pats, we consider the impact of aitached regulatory proteins on the so-called breathers or bubbles, Assuming that 7 idal gus of bubbles may exist in the DNA chain at physiofogial temperatures we adopt a Statistical approach fo calculate the average size of base-pair strecing under the prevailing conditions DOK: 10.1103/PhysRevE 65,081901 L INTRODUCTION Deoxyribonucleic acid (DNA) is doubtlessly the most im- portant biomolecule. Its double stranded helical structure un- dergoes a very complex dynamics and the knowledge ofthat dynamics provides insights into various related biological phenomena, such as tanscriptioa, translation, and mutations. The key problem in DNA biophysics is how to relate fune- tional properties of the DNA with its structural and physical dynamical characteristics. In this paper our aim is to estab- lish a plausible relationship between the regulation of tran- scription processes and the nonlinear dynamics of DNA. The possibilty thet nonlinear effects might concentrate the vibrational energy of DNA into localized solitonlike ob- jects was first contemplated by Englander etl. (1, AL though several authors [2-9] have suggested that either to- pological Kink solitons or bell-shaped breathers would be good candidates to play a basic ole in the DNA nonlinear dynamics, there are still several unresolved questions in this regard. The hierarchy of the most important models for non- linear DNA dynamics was presented by Yakushevich [10] In the present paper we have strongly relied on the ex- tended model for DNA dynamics, fist proposed by Peyrard and Bishop [7]. In the following, we fist outline the main foatures of that model, which will be henceforth referred to as the PB model for short. In that context we have examined in detail the necessary conditions for the existence of breather excitations in DNA chains. We then focus our atten- tion on the very important biophysical situation where the breather solution of the PB model is suspected of playing the role of @ conformational agent in the process of gene expres- sion. In that respect, the impact of regulatory proteins on breather dynamics was examined by the method of nonequi- librium statistical physies allowing the calculation of an av- erage stretching distance of the base pairs involved “The present paper is organized in the following way. In See. I, for clarity and coneiseness we outline the PB model primarily proposed to describe the process of local opening, of DNA base pairs (or local melting of the double helix), ‘Then we have attempted to shed more light on the still some- what vayue parameter values of the PB model. This is im portant in the determination of the necessary conditions for the existence of breather solitons. in Sec, Il, we present one 1063-651X?2002/65(5)!081901(10)820.00 65.051901-1 PACS number(s): 87.15. ~, 82.39, $2.39 Fk, 52.35.) class of specific regulatory proteins, which are attached by hydrogen bonds to a DNA chain. We conjecture that these proteins, possessing a well-known carbon oxide stretching ‘mode could resonantly impact on the DNA dynamics in- creasing the magnitude of stretching base pairs involved in the breather’s dynamics. In Sec. IV we present a discussion and conclusions regarding the feasibility of this approach in explaining the role of regulatory proteins in controlling gene expression, Il. THE PHYSICAL CONCEPT OF THE PB MODEL INDNA The B-form DNA in the Watson-Crick model [11] is a double helix consisting of two strands By and B, (see Fig. 1) with the characteristic dimensions depicted, Molecular ‘masses of nucleotides (considered without adjacent sugar groups) range from 340 (cytosine) to 380 mu (guanine) ‘Therefore, itis apparent thatthe four constituent bese mucle- otides (adenine, cytosine, guanine, and thymine) do not di fec in their mass by more than 13%, thus inhomogenities due to the base sequences are usually ignored in biophysical models of DNA dynamics, FIG. 1. Sketch of the double heli. The sugar-phospate back- bone is shown as ribbons. The bases are depicted as short transverse rods 2002 The American Physical Society M. V. SATARIC AND J. A. TUSZYNSKT © *, i FIG. 2, (a) Schematic representation ofthe displacements in the DNA lattice: (b) the corresponding Morse poteatial between base pairs; and (¢) 2 bubble defect. Consequently, 2 common mass M is used for the bascs, and the samne coupling constant k for the nearest-neighbor hharmonie interactions along cach strand is assumed, see Fig. 2a, “The strands are coupled to each other through hydrogen bonds that are supposed to be responsible for transverse dis- placements of base pairs. According to the rule of Chargaft tind co-workers {12] there ae only two types of base pais in DNA; A-T and G-C pais, se Fig. 3. An 4-T pair is linked by two, while G-C pair consists of thiee hydrogen bonds. Hence. hydrogen bond variability in DNA exhibits more Conspicuous inhomogenity than the corresponding mass dis- tribution ‘Nonetheless, this inhomogenity is neglected in the PB aodel and the hydrogen bond interactions are averaged cut fand modeled by the Morse potential (see Fig. 2(b)}- The three-dimensional helicoidal structure of the DNA chain im- plies that neighboring base nucleotides from different stands bre sufficiently close to interact through water filaments. This PHYSICAL REVIEW E 65 051901 thymine cytosine guanosine € | | FIG. 3. Base pairs: (8) A-T and (6) G-C. Hydrogen atoms that ‘are substituted in DNA for carbon atoms of sugar rings are marked by asterisks | reans that a base atthe site n of one strand, interacts with both the (n+ 4)th and the (n—4)th bases ofthe other strand, Introducing the transverse displacements u,, Yq, of the bases from their equilibrium positions along the direction of ‘hydrogen bonds the PB Hamiltonian (13] for the DNA cain is given in the form +Dleut=o(.-v0}-1} Qn ‘As already mentioned, M stands for the mass of a base nucleotide, Px, = Mit, and P,q= Mu, are the base moment, (or K) is the harmonic elastic constant of the longitudinal (or helicoidal) springs. Finally, D and a are the depth and the inverse width of the Morse potential well, respectively [see Fig. 2(b)} . tis more convenient to describe the transversal motion of the two DNA strands in terms of the center-of-mass coordi nates representing the in-phase and ouCof;phase transversal ‘motions Just = u,- er Ce ‘The dynamical equations of motion derived from the Hamil- tonian (2.1) are then Mig = KRtpe yt hye 2n) +A Cg sa tka a 28a) He ea) 051901-2 IMPACT OF REGULATORY PROTEINS ON THE Mig Knot Yet 209)“ KU ete t Pane t 20 9) + 2WhaD(eW Pe 1) (Qa) Equation (2.3) describes the well-studied linear waves (phonons) while Eq. (2.4) yields nonlinear solicontike bresth- ers. Consequently, we pay close attention to the nonlinear Fa, (24) bearing in mind that a stable breather solution may be viewed as 2 candidate for long-range interactions along DNA chains ‘According to the original approach of Ref. [13] itis as- sumed thatthe oscillations of bases arc large enough to be anharmonic, but still insuicient to break the bond since the plateau of the Morse potential is not yet reached, Thus, it is presutned thatthe base nucleotides oscillate around the bot tom of the Morse potential allowing the following transfor snation to be safely implemented re 3) Equation (2.4) can now be expanded to fourth order terms. jn ¢, resulting in the following form: 6,-4 ,-,-20,)-* Fy Pass Dyn 2P_)— Fp (Ppee Dyet2P,) —wi(,+ cad} + 2B d})—---, (2.6) where the new notation is introduced as 4a°D or an Note that Eg. (2.6) possesses two time scales. The first one corresponds to the vibrations of the nucleotide around its ‘equilibrium position and the second, much larger, to the ‘propagation of a collective coherent structure along the DNA chain, Therefore, one can safely apply the reductive pert bation method expanding in the small parameter ¢ and using ‘2 semidiserete approximation [14]; =F ent ete" + efFylentyet) +LF (en bere?" + 6.6.4 (2) and O,=nge- at. (28) Here, wo represents the optical frequency of the base-pair vi brations, € is the distance hetween neighboring bases in the same strand, and q is the wave number whose role will be discussed later. ‘Now we consider a continuum limit via a multiple-scale expansion, where ge, THe 29 ‘This means that the nonlinear excitation that emerges in this, picture consists of a carrier wave modulated by a slowly PHYSICAL REVIEW E 65 051901 varying envelope. The expansion Eq. (2.8) together with the sealing in Eq, (2.9) yield the following continuum approxi mation transformations: FU £ VF (Z,T) FZ, Tel + PA Z.T) ere? PUn24) FULTS Bet + TFA Z,TOCE and D9 (PF pp DieoP yy— WF e+ For 1 (OF app MC WF yy A€u Fy)? +66, 2.10) where Fz and Fy stand for the corresponding derivatives with respect to the new variables Z and 7, etc. Following rather tedious algebra, we obtain & set of important relations from Eq. (2.6). Equating the coefficients for the frst har- monic (e'°*) one obtains OF py DiewF oF k ig 2F ileos(g¢)—1]+ ee Fyzsin(ge) K + BAR zp costgt)) ~ 5 (2FiLeost4ge) + 1] + 4iet Fy sin(4qe)+ 162 CF zz 09(490)} ull Fy 2 Rak oF +20F TF 24 3A1F PF] uy) ‘After neglecting all the tems with ¢ in Eq. (2.11) a disper sion relation is found to be in the following form: > 2k 2K [ecosige)— 1+ Fy Leoe(490)+1] eM (2.12) From Eq, (2.12) one obtains the group velocity for the wave packet as (2.13) € Yen ppglksinae)~ 4k sin'4g0)] Equating the coefficients for e!" and ¢2" we fink the fumetions Fy, Fy, and F as follows: = KIF P, Fy= OF), (14) where le B 2a 2.18) {a+ 4k | ae i () ina3! Thus, taking into account Eq. (2.14), then again introdue- ing new independent variables 981901-3

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