Classical molecular mechanics methods

In general, the conformational energy map shows that only a limited portion of the total (p, f conformation space is actually accessible to the dissaccharide at room temperature. The dissaccharide is not frozen into its lowest energy conformation, nevertheless the steep walls of the allowed region of conformational energy may dramatically limit the multiplicity of thermally accessible conformational states. 

One useful method, for taking into account the effect of solvent media upon the conformational properties of glycosidic structures, is the continuum reaction field method. This method is based on the Scaled Particle Theory (SPT) equations and on Onsager s theory of the reaction field, as applied by Abraham by considering the solvent as a dielectric continuum. In this approach the total conformational energy, Gt t, is given by  

It is noteworthy fliat Gea, is a function solely of solvent density and solvent and solute dimensions and represents a measure of the cohesive forces among solvent molecules. In a given solvent, this conlribution is a function of die radius of solute molecule which may differ remarkably as a function of dihedral angles tp and / only. 

The electrostatic interaction term between solute and solvent is based on the con- 

The free energy of dispersion, Gjjisp, in equation [12.2.2] takes into account both attractive and repulsive non-bonding interactions and is expressed as a combination of the London dispersion equation and Bom-type repulsion  

N is the number of molecules surrounding the solute molecule in a given conformation and is calculated from the following equation  

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The extended Electron Distribution (XED) force field was first described by Vinter [96]. This force field proposes a different electrostatic treatment of molecules to that found in classical molecular mechanics methods. In classical methods, charges are placed on atomic centers, whereas the XED force field explicitly represents electron anisotropy as an expansion of point charges around each atom. The author claims that it successfully reproduces experimental aromatic ji stacking. Later, others made similar observations [97]. This force field is now available in Cresset BioMoleculaf s software package [95]. Apaya et al. were the first to describe the applicability of electrostatic extrema values in drug design, on a set of PDE III inhibitors [98]. 

Modelling molecular structures, (Wiley, 1996) by A. Hinchliffe is a general introductory text about the use of classical ( molecular mechanics ) methods as well as both semi-empirical and ab initio quantum-mechanical methods of computing molecular structures. 

Molecular mechanics simulations use the laws of classical physics to predict the structures and properties of molecules. Molecular mechanics methods are available in many computer programs, including MM3, HyperChem, Quanta, Sybyl, and Alchemy. There are many different molecular mechanics methods. Each one is characterized by its particular/orce eW. A force field has these components ... 

The examples cited above are of molecules which are not strictly speaking noorigid, although they have more than one well-defined equilibrium configuration. The 1,2-dichloroetbane molecule discussed above is a classic example. With the aid of computer programs that have been developed to treat this problem, it has become possible to calculate wifi) confidence the equilibrium conformations of such molecules, as well as the energy differences and the tunneling barriers between them. It is appropriate here to summarize briefly the so-called molecular mechanics method that is currently employed to obtain these results. 

Theoretical models include those based on classical (Newtonian) mechanical methods—force field methods known as molecular mechanical methods. These include MM2, MM3, Amber, Sybyl, UFF, and others described in the following paragraphs. These methods are based on Hook s law describing the parabolic potential for the stretching of a chemical bond, van der Waal s interactions, electrostatics, and other forces described more fully below. The combination assembled into the force field is parameterized based on fitting to experimental data. One can treat 1500-2500 atom systems by molecular mechanical methods. Only this method is treated in detail in this text. Other theoretical models are based on quantum mechanical methods. These include ... 

Molecular mechanics methods achieve good structural accuracy for classical molecules, whereas their reliability for species with particular combinations of atoms may be questionable, particularly for molecules containing heteroatoms, which affect geometry and conformation via the position of their lone-pairs. Force-field programs, for example, often fail to calculate the geometry... 

These approaches may include (1) purely empirical methods that try to simulate conformations by using classical molecular mechanics and adjustable parameters, still employed in very large molecular systems (2) potential energy determination with empirical and semiempirical functions consisting... 

This presentation is structured in the following way. The first section outlines the procedure for the quantum mechanics and classical mechanics approach. The following two sections contain an overview of how to establish a density functional theory and molecular mechanics method along with the theoretical background for... 

Most molecular modeUing packages allow the use of empirical methods which only consider the nuclei. These are called molecular mechanical methods and are faster than the quantum-mechanical methods. They are based on classical mechanics and therefore allow treatment of larger molecules. However, as electrons are not included in the calculation, this approach does not provide information on bond breaking or formation, or any details of orbitals involved in any interactions. 

By far the major computational quantum mechanical method used to compute the electronic state in Car-Parrinello simulations is density-functional theory (DFT) (Hohenberg and Kohn, 1964 Kohn and Sham, 1965 Parr and Yang, 1989). It is the method used originally by Roberto Car and Michele Parrinello in 1985, and it provides the highest level of accuracy for the computational cost. For these reasons, in this section the only computational quantum mechanical method discussed is DFT. Section A consists of a brief review of classical molecular dynamics methods. Following this is a description of DFT in general (Section B) and then a description of practical DFT computations of chemical systems using the plane-wave pseudopotential method (Section C). The section ends with a description of the Car-Parrinello method and some basic issues involved in its use (Section D). 

The present contribution concerns an outline of the response tlieory for the multiconfigurational self-consistent field electronic structure method coupled to molecular mechanics force fields and it gives an overview of the theoretical developments presented in the work by Poulsen et al. [7, 8, 9], The multiconfigurational self-consistent field molecular mechanics (MCSCF/MM) response method has been developed to include third order molecular properties [7, 8, 9], This contribution contains a section that describes the establisment of the energy functional for the situation where a multiconfigurational self-consistent field electronic structure method is coupled to a classical molecular mechanics field. The second section provides the necessary background for forming the fundamental equations within response theory. The third and fourth sections present the linear and quadratic, respectively, response equations for the MCSCF/MM response method. The fifth 283... 

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