Molecular dynamics programming techniques

In this review, we shall focus on the development and application of combined QM/MM potentials in condensed phase simulations where solute and solvent molecules are explicitly treated, in both aqueous and organic environments. The emphasis of this chapter is the use of molecular orbital (MO) theory in the QM treatment because it is well documented and familiar to chemists. Details of the Monte Carlo and molecular dynamics simulation techniques are available in an excellent book by Allen and Tildesley. In a recent paper, Aqvist and Warshel provided a number of additional details of the methodology, particularly on the use of the EVB method. We have also benefited both intellectually and technically from the thorough paper by Field, Bash, and Karplus, which gives additional insights on the implementation of combining molecular orbital and molecular mechanics programs. 

Molecular dynamics consists of the brute-force solution of Newton s equations of motion. It is necessary to encode in the program the potential energy and force law of interaction between molecules the equations of motion are solved numerically, by finite difference techniques. The system evolution corresponds closely to what happens in real life and allows us to calculate dynamical properties, as well as thennodynamic and structural fiinctions. For a range of molecular models, packaged routines are available, either connnercially or tlirough the academic conmuinity. 

The input to a minimisation program consists of a set of initial coordinates for the system. The initial coordinates may come from a variety of sources. They may be obtained from an experimental technique, such as X-ray crystallography or NMR. In other cases a theoretical method is employed, such as a conformational search algorithm. A combination of experimenfal and theoretical approaches may also be used. For example, to study the behaviour of a protein in water one may take an X-ray structure of the protein and immerse it in a solvent bath, where the coordinates of the solvent molecules have been obtained from a Monte Carlo or molecular dynamics simulation. 

Combined Quantum and Molecular Mechanical Simulations. A recentiy developed technique is one wherein a molecular dynamics simulation includes the treatment of some part of the system with a quantum mechanical technique. This approach, QM/MM, is similar to the coupled quantum and molecular mechanical methods introduced by Warshel and Karplus (45) and at the heart of the MMI, MMP2, and MM3 programs by AUinger (60). These latter programs use quantum mechanical methods to treat the TT-systems of the stmctures in question separately from the sigma framework. 

The credit load for die computational chemistry laboratory course requires that the average student should be able to complete almost all of the work required for the course within die time constraint of one four-hour laboratory period per week. This constraint limits the material covered in the course. Four principal computational methods have been identified as being of primary importance in the practice of chemistry and thus in the education of chemistry students (1) Monte Carlo Methods, (2) Molecular Mechanics Methods, (3) Molecular Dynamics Simulations, and (4) Quantum Chemical Calculations. Clearly, other important topics could be added when time permits. These four methods are developed as separate units, in each case beginning with die fundamental principles including simple programming and visualization, and building to the sophisticated application of the technique to a chemical problem. 

After 14 years on the faculty of Imperial College, Jacobs moved from London, England, to London, Ontario, where his research program focused on the optical and electrical properties of ionic crystals, as well as on the experimental and theoretical determination of thermodynamic and kinetic properties of crystal defects.213 Over the years his research interests have expanded to include several aspects of computer simulations of condensed matter.214 He has developed algorithms215 for molecular dynamics studies of non-ionic and ionic systems, and he has carried out simulations on systems as diverse as metals, solid ionic conductors, and ceramics. The simulation of the effects of radiation damage is a special interest. His recent interests include the study of perfect and imperfect crystals by means of quantum chemical methods. The corrosion of metals is being studied by both quantum chemical and molecular dynamics techniques. 

Peter Kusalik took up an appointment at Dalhousie University in 1989 and developed a research program focused on computer simulation studies of molecular liquids, solids, and solutions. As well as standard simulation approaches, he has explored nonequilibrium molecular dynamics techniques and applied field simulations, the development of new models and methodologies being one aim of his research. A common focus throughout his work has been the examination of the interplay between microscopic structure and dynamics in condensed matter and their relationship to bulk properties. 

A different approach to the structural problem is provided by the technique of computerized molecular dynamics. It is now possible to set up in a computer program a microcanonical ensemble of perhaps two... 

There have been some molecular dynamics simulations with anisotropic atom-atom potentials, the earliest being simulations with chlorine poten-tials. " Those simulations demonstrated that the computer time requirements were quite reasonable, and the results were effective compared with the inclusion of additional isotropic sites. The technique has also been extended to butane by means of a four-site anisotropic carbon model. A general DMA based potential model is being implemented into the new CCP5 molecular simulation program DL POLY. Monte Carlo simulations can use anisotropic atom-atom potentials readily, " since the calculations require the evaluation of only the energy. 

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