Molecular dynamics simulations force field

In MD, a force field is used to calculate the forces on each atom of the simulated system. Then, following Newtonian mechanics, velocities and accelerations are calculated, and the atoms are slightly moved with respect to a given time step. Introducing molecular dynamics and force fields is clearly beyond the scope of this chapter, so we refer the reader to earlier reviews in this book series.118-123 However, some aspects of docking based on MD simulations should be briefly mentioned. 

Molecular dynamics simulation package with various force field implementations, special support for AMBER. Parallel version and Xll trajectory viewer available. http //ganter.chemie.uni-dortmund.de/MOSCITO/... 

Rappe A K, C J Casewit, K S Colwell, W A Goddard III and W M Skiff 1992. UFF, a Full Periodic Table Force Field for Molecular Mechanics and Molecular Dynamics Simulations. Journal of the American Chemical Society 114 10024-10035. 

The Merck molecular force field (MMFF) is one of the more recently published force fields in the literature. It is a general-purpose method, particularly popular for organic molecules. MMFF94 was originally intended for molecular dynamics simulations, but has also seen much use for geometry optimization. It uses five valence terms, one of which is an electrostatic term, and one cross tenn. 

Force field calculations often truncate the non bonded potential energy of a molecular system at some finite distance. Truncation (nonbonded cutoff) saves computing resources. Also, periodic boxes and boundary conditions require it. However, this approximation is too crude for some calculations. For example, a molecular dynamic simulation with an abruptly truncated potential produces anomalous and nonphysical behavior. One symptom is that the solute (for example, a protein) cools and the solvent (water) heats rapidly. The temperatures of system components then slowly converge until the system appears to be in equilibrium, but it is not. 

Before running a molecular dynamics simulation with solvent and a molecular mechanics method, choose the appropriate dielectric constant. You specify the type and value of the dielectric constant in the Force Field Options dialog box. The dielectric constant defines the screening effect of solvent molecules on nonbonded (electrostatic) interactions. 

Molecular Dynamics and Monte Carlo Simulations. At the heart of the method of molecular dynamics is a simulation model consisting of potential energy functions, or force fields. Molecular dynamics calculations represent a deterministic method, ie, one based on the assumption that atoms move according to laws of Newtonian mechanics. Molecular dynamics simulations can be performed for short time-periods, eg, 50—100 picoseconds, to examine localized very high frequency motions, such as bond length distortions, or, over much longer periods of time, eg, 500—2000 ps, in order to derive equiUbrium properties. It is worthwhile to summarize what properties researchers can expect to evaluate by performing molecular simulations ... 

We have presented a simple protocol to run MD simulations for systems of interest. There are, however, some tricks to improve the efficiency and accuracy of molecular dynamics simulations. Some of these techniques, which are discussed later in the book, are today considered standard practice. These methods address diverse issues ranging from efficient force field evaluation to simplified solvent representations. 

At a first glance, it is tempting to perform a full-scale MD (molecular dynamics) simulation, which includes all the chemical detail of the system under consideration. Starting from a detailed force field U R), Newton s equations of motion... 

The principle of the molecular dynamics simulation approach is the movement of atoms under the action of a force field. 

Importantly, all biological procedures are operating at a temperature of 310 Kelvin, not at 0 Kelvin as the potential energy is calculated by the force fields. The kinetic energy must also be considered. Molecules and proteins at room temperature change the conformation at least at the surface and in loop region. Molecular dynamics simulation (MD) is an approach to tackle these kinetic and stability problems. 

It is worth noting that much of the development work for the MM force fields has centred on low energy structures of molecules. Consequently, some of the force constants are less applicable to higher energy molecular structures that can occur in molecular dynamics simulations of liquid crystals. 

The rapid rise in computer speed over recent years has led to atom-based simulations of liquid crystals becoming an important new area of research. Molecular mechanics and Monte Carlo studies of isolated liquid crystal molecules are now routine. However, care must be taken to model properly the influence of a nematic mean field if information about molecular structure in a mesophase is required. The current state-of-the-art consists of studies of (in the order of) 100 molecules in the bulk, in contact with a surface, or in a bilayer in contact with a solvent. Current simulation times can extend to around 10 ns and are sufficient to observe the growth of mesophases from an isotropic liquid. The results from a number of studies look very promising, and a wealth of structural and dynamic data now exists for bulk phases, monolayers and bilayers. Continued development of force fields for liquid crystals will be particularly important in the next few years, and particular emphasis must be placed on the development of all-atom force fields that are able to reproduce liquid phase densities for small molecules. Without these it will be difficult to obtain accurate phase transition temperatures. It will also be necessary to extend atomistic models to several thousand molecules to remove major system size effects which are present in all current work. This will be greatly facilitated by modern parallel simulation methods that allow molecular dynamics simulations to be carried out in parallel on multi-processor systems [115]. 

DG was primarily developed as a mathematical tool for obtaining spahal structures when pairwise distance information is given [118]. The DG method does not use any classical force fields. Thus, the conformational energy of a molecule is neglected and all 3D structures which are compatible with the distance restraints are presented. Nowadays, it is often used in the determination of 3D structures of small and medium-sized organic molecules. Gompared to force field-based methods, DG is a fast computational technique in order to scan the global conformational space. To get optimized structures, DG mostly has to be followed by various molecular dynamic simulation. 

Equation (4-5) can be directly utilized in statistical mechanical Monte Carlo and molecular dynamics simulations by choosing an appropriate QM model, balancing computational efficiency and accuracy, and MM force fields for biomacromolecules and the solvent water. Our group has extensively explored various QM/MM methods using different quantum models, ranging from semiempirical methods to ab initio molecular orbital and valence bond theories to density functional theory, applied to a wide range of applications in chemistry and biology. Some of these studies have been discussed before and they are not emphasized in this article. We focus on developments that have not been often discussed. 

Liu YP, Kim K, Berne BJ, Friesner RA, Rick SW (1998) Constructing ab initio force fields for molecular dynamics simulations. J Chem Phys 108f 12) 1739 1755... 

Patel S, Mackerell AD, Brooks CL (2004) CHARMM fluctuating charge force field for proteins II -Protein/solvent properties from molecular dynamics simulations using a nonadditive electrostatic model. J Comput Chem 25(12) 1504-1514... 

Patel S, Brooks CL (2005) A nonadditive methanol force field bulk liquid and liquid-vapor interfacial properties via molecular dynamics simulations using a fluctuating charge model. J Chem Phys... 

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