Molecular modelling, chemical reaction

The main purpose of this chapter is to present the basics of ab initio molecular dynamics, focusing on the practical aspects of the simulations, and in particular, on modeling chemical reactions. Although CP-MD is a general molecular dynamics scheme which potentially can be applied in combination with any electronic structure method, the Car-Parinello MD is usually implemented within the framework of density functional theory with plane-waves as the basis set. Such an approach is conceptually quite distant from the commonly applied static approaches of quantum-chemistry with atom-centered basis sets. Therefore, a main... 

Standard molecular mechanics (MM) force fields have been developed that provide a good description of protein structure and dynamics,21 but they cannot be used to model chemical reactions. Molecular dynamics simulations are very important in simulations of protein folding and unfolding,22 an area in which they complement experiments and aid in interpretation of experimental data.23 Molecular dynamics simulations are also important in drug design applications,24 and particularly in studies of protein conformational changes,25,26 simulations of the structure and function of ion channels and other membrane proteins,27-29 and in studies of biological macromolecular assemblies such as F-l-ATPase.30... 

Quantum chemical methods aim to treat the fundamental quantum mechanics of electronic structure, and so can be used to model chemical reactions. Such quantum chemical methods are more flexible and more generally applicable than molecular mechanics methods, and so are often preferable and can be easier to apply. The major problem with electronic structure calculations on enzymes is presented by the very large computational resources required, which significantly limits the size of the system that can be treated. To overcome this problem, small models of enzyme active sites can be studied in isolation (and perhaps with an approximate model of solvation). Alternatively, a quantum chemical treatment of the enzyme active site can be combined with a molecular mechanics description of the protein and solvent environment the QM/MM approach. Both will be described below. 

The premise of molecular biology is that cellular processes are governed by physico-chemical principles, and accordingly, those principles may be used to translate known or hypothetical molecular mechanisms to mathematical equations. In this section, the general principles of chemical kinetics, mass transport, and fluid mechanics used to model chemical reaction systems are reviewed briefly. 

Standard molecular mechanics (MM) methods (e.g. the popular force fields developed for AMBER, CHARMM and GROMOS decribed in Section 2 above) provide a good description of protein structure and dynamics, but cannot be used to model chemical reactions. This limitation is due their simple functional forms (e.g. harmonic terms for bond stretching) and inability to model changes in electronic polarization (because of the invariant point partial atomic charge used by these molecular mechanics methods to represent electrostatic interactions). 

Modeling of the molecular diffusion-chemical reaction processes to predict the local reaction rate. 

Ken Jordan received his Ph.D. in physical chemistry in 1974 under the direction of Bob Silbey at MIT. He then joined the Department of Engineering and Applied Science, Yale University, as a J.W. Gibbs Instructor, being promoted to Assistant Professor in 1976. In 1978 Professor Jordan moved to the Chemistry Department at the University of Pittsburgh where he is now Professor and Director of the Center for Molecular and Materials Simulations. His interest in the application of computers to chemical problems stems from his graduate student days. Professor Jordan s recent research has focused on the properties of hydrogen-bonded clusters, modeling chemical reactions on surfaces, electron-induced chemistry and the development of new methods for Monte Carlo simulations. 

Predictions of the kinetics of electrons taking into account all size-dependent factors are possible only when adeqnate ion-molecular models of reaction layers are bnilt. For a number of systems, this problem can be solved snccessfully by employing qnantum-chemical methods based on quantum mechanical theory of the charge-transfer elementary act [74,75] along with the classical effects of the cation size, which are manifested in the rednction of anions on a negatively charged snrface [74,75]. 

Margitfalvi, J.L., Tfirst, E., Hegedus, M., Talas, E. (1998) Enantioselective hydrogenation of alpha-keio esters over cinchona-Pt-Alumina catalysts. Kinetic and molecular modeling, Chemical Industries Series (Catalysis of Organic Reactions, Herkes, F.E., ed.) (Dekker) 75, 531-542. 

Computer-Assisted Structure Elucidation Modelling Chemical Reaction Sequences Used in Molecular Structure Problems... 

The results discussed here contain a wealth of dynamical details of the detonation wave profiles under different conditions. In particular, they show both thermal initiation and shock initiation of dissociation reactions, as well as the coupling of the reactions front, the shock front, and the thermoelastic properties of the lattice, all under highly nonequilibrium conditions. It is true that our hypothetical molecular model and the simulation of the "chemistry" of dissociation are too simple and perhaps simplistic. Nevertheless, because we were able to demonstrate by separate tests [36,37] that this model system was well behaved, we believe that many of the details, especially those relating to the mechanisms and rates of energy transfer and energy sharing, should have their counterparts in reality. As we further develop our techniques of modeling chemical reactions, we should be able to apply the MD method to the study of these details which are not easily accessible by any other method. 

Motivated by this recent interest in monolayer lubricants, molecular dynamics (MD) simulations have been used to examine monolayers of w-alkanes that are chemically bound or anchored to diamond substrates. A new empirical-potential energy function, which is capable of modeling chemical reactions in hydrocarbons of all phases, has been developed for this work (15). A single-wall, capped armchair nanotube is used to indent these hydrocarbon monolayers and to investigate friction. The effects of tip flexibility and tip speed on indentation and friction are examined. Particular attention will be paid to the formation of defects and bond rupture (and formation) during the course of the simulations. Previous MD simulations have examined the structure (16-18) and compression of -alkanethiols on Au (19,20). The major difference between those studies and the work discussed here is that irreversible chemical changes (or changes in hybridization associated with bond rupture and formation) are possible in these studies. 

Molecular level Elementary reactions Molecular modeling Chemical equilibrium... 

Therefore, quantum molecular dynamics simulations will generate the most detailed modeling of interatomic interactions as electrons are the basis of aU such interactions. Quantum simulations allow for certain phenomena like electron transport within a system to be modeled, which cannot be modeled in force-field or coarse grain molecular dynamics simulations because they do not explicitly model electrons. Also, in order to model chemical reactions, quantum simulations are the most accurate approach (Note there have been force-field and coarse-grain molecular dynamics simulations that have modeled the formation and breaking of bonds, but some a priori knowledge must then be included in the model to allow for the reaction to take place). The major limitations of quantum simulations is that the simulations are very computationally intensive, which results in the capability to model only small system sizes ( 10 particles) and time s). Thus the systems that can be modeled are limited to... 

In this chapter. Dihydrofolate reductase (DHFR) has been selected as a conductor wire to present the evolution and difficulties to model chemical reactions in enzymes, from the early calculations based at semiempirical level, carried out in gas phase, to the more sophisticated simulations based on hybrid Quantum Mechanical/Molecular Mechanics (QM/MM) schemes [21, 22]. DHFR offers an... 

Modelling chemical reactions naturally falls into a field of molecular dynamics, such as the reactive models presented by Buehler. However, the typical time scale... 

Gao and coworkers proposed the X-Pol framework by combining the fragment-based electronic structure theory with a molecular mechanical force field. Unlike the traditional force fields, X-Pol does not require bond stretching, angle, and torsion terms because they are represented explicitly by quantum mechanics. The polarization and charge transfer between fragments are also evaluated quantum mechanically. Furthermore, X-Pol can be used to model chemical reactions. 

Although a separation of electronic and nuclear motion provides an important simplification and appealing qualitative model for chemistry, the electronic Sclirodinger equation is still fomiidable. Efforts to solve it approximately and apply these solutions to the study of spectroscopy, stmcture and chemical reactions fonn the subject of what is usually called electronic structure theory or quantum chemistry. The starting point for most calculations and the foundation of molecular orbital theory is the independent-particle approximation. 

Hydrogen-bonded clusters are an important class of molecular clusters, among which small water clusters have received a considerable amount of attention [148, 149]. Solvated cluster ions have also been produced and studied [150, 151]. These solvated clusters provide ideal model systems to obtain microscopic infonnation about solvation effect and its influence on chemical reactions. 

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