computer modeling in molecular biology.pdf

108 E. WesthoJ C. Rubin-Carrez, and K FritschThe description above implies that the main theoretical bottleneck in MD simulationsof nucleic acids resides in the treatment of the electrostatics and of the solvent(water molecules and counter ions). In an aqueous solution, two charges are screenedfrom one another by two distinct effects, the local water structure or orientation ofwater dipoles and the effect of other ions. Macroscopically, these two effects arehandled respectively by the dielectric constant and the Debye-Huckel screened potential.In MD simulations, two paths have been followed: either the macroscopic onewith an implicit treatment of the solvent effects or the microscopic one with an explicitatomic description of the solvent molecules.5.5 Implicit Treatment of the SolventTheoretically, the implicit approach is the least satisfying, since it blends an atomisticdescription of the solute with a macroscopic treatment of the solvent. Besides, it isgenerally based on a distance-dependent “dielectric constant” E (r) in the termdescribing electrostatic interactions.The peculiarities of a distance-dependent dielectric function are well described byRogers [MI. However, despite those caveats, several dielectric functions have beensuggested and used because of the tremendous reduction in computer time and thesimplicity of the calculations. The most common ones are those offered by theprogram AMBER where E (r) = a or E (r) = ar with a a scalar, usually equal to either1 or 4. Such functions, however, do not take into account dielectric saturation of thewater dipoles, since they are either constant or increase linearly with distance.Recently, two other dielectric functions which include dielectric saturation have beenintroduced in MD simulations, one for proteins and another one mainly for nucleicacids (Figure 5-1). The one suggested by Mehler and Eichele [19] has the followingform :BE (r) = A +1 + ke-*BrA = -20.929, B = &H2o -A, I = 0.001787, k = 3.4781, &Hzo = 78.4We have used the sigmoidal dielectric function proposed by Lavery et al. [20] andwe modified the program AMBER to allow the use of this distance dependent functionwhich has the form:D-1E (r) = D --2((Ar)’ + 2Ar + 2) e-Ar