Visual Molecular Dynamics Model

Visual Molecular Dynamics Model (Humphrey et al., 1996) of BSA from Protein Data Bank ID 4F5S (Bujacz. 2012) determined at 2.47 A resolution by X-ray diffraction. 

Good semi-quantitative agreements are found in diffraction patterns and proposed models obtained by molecular-dynamics[14], because the results of the ex-periments[31-34] are consistent with the atomic models proposed by us[14]. However, in the present state of high-resolution electron microscopy, taking into account, moreover, the number of sheets and the complicated geometry of the helix, it seems unlikely to directly visualize the pentagon-hexagon pairs. 

The molecular dynamics unit provides a good example with which to outline the basic approach. One of the most powerful applications of modem computational methods arises from their usefulness in visualizing dynamic molecular processes. Small molecules, solutions, and, more importantly, macromolecules are not static entities. A protein crystal structure or a model of a DNA helix actually provides relatively little information and insight into function as function is an intrinsically dynamic property. In this unit students are led through the basics of a molecular dynamics calculation, the implementation of methods integrating Newton s equations, the visualization of atomic motion controlled by potential energy functions or molecular force fields and onto the modeling and visualization of more complex systems. 

Whilst these difficulties do not invalidate application of molecular mechanics methods to such systems, they do mean that the interpretation of the results must be different from what is appropiate for small-molecule systems. For these reasons, the real value of molecular modeling of macromolecule systems emerges when the models are used to make predictions that can be tested experimentally or when the modeling is used as an adjunct to the interpretation of experiments. Alternatively, the relatively crude molecular mechanics models, while not of quantitative value, are an excellent aid to the visualization of problems not readily accessible in any other way. Molecular dynamics is needed, especially for large molecules, to scan the energy surface and find low-energy minima. The combination of computational studies with experimental data can help to assign the structure. 

To perform the design of new molecules based on the approaches described above, powerful computer-aided tools are required. These include molecular modeling tools for visualization and analysis, extraction of 3D structures from databases, construction of 3D models using force fields [77-79] and molecular dynamics methods, docking of 3D models to protein cavities. These methods have been documented in detail in the previous volumes of this series and in a number of recent review articles [80-87]. These will therefore only be discussed in the context of the case studies presented in this volume. 

Larger molecules, however, like proteins contain too many rotational bonds which affords other methods like molecular dynamics (MD) to find energy minimum structures. This technique involves a molecular motion as result of a given temperature. The computational basis still is on the molecular mechanics level and the atomic movement is followed by snap shots of atom coordinates and of the corresponding energies along a femtosecond to nanosecond timeline, which in turn can be visualized by suitable molecular modeling techniques. 

Photoisomerization.—Birge and Hubbard analyse the molecular dynamics of cis-trans isomerization in the visual pigment rhodopsin using INDO-CISD molecular orbital theory and semiempirical molecular dynamic theory. The analysis predicts that the excited-state species is trapped during isomerization in an activated complex that has a lifetime of 0.5ps. This activated species oscillates between two components which preferentially decay to form isomerized product (bathorhodopsin) or unisomerized 11-cw-chromophore (rhodopsin) within 1.9—2.3ps. The authors further conclude that the chromophore in bathorhodopsin has a distorted all-rraw-geometry and is the most realistic model for the first intermediate in the bleaching cycle of rhodopsin. 

A good model of the electrolyte must describe the ions, solvent molecules and their orientation at the molecular level. Molecular dynamics simulations that are performed to visualize the orientation of the electrolyte molecules in the vicinity of the electrode surface are based on a set of parameters that can be varied in order to best described the properties of the system under investigation. The most reasonable models for solvent-solvent and ion-solvent interactions consider distribution of point charges on solvent molecules and take into account Lennard-Jones-type potentials that are strongly repulsive at short distances. Molecular dynamics simulations are typically performed on a system confined between two metal electrodes and the number of confined ions and solvent molecules is often limited by the computing power of modem computers. Some representative examples of results of such calculations are given in ref 60,63-68. 

Little has been said here about computer graphics, but its importance to the birth of molecular modeling should not be underestimated. Energy calculations, whether molecular mechanics, molecular dynamics, quantum mechanics, or whatever, generate an enormous amount of data. Computer graphics (or visualization, as it has come to be called lately) renders all that data manageable and assimilable. 

---