Simulation large molecular systems

Computational chemistry attempting to simulate large molecular systems... 

Chapter 6 - Computational chemistry Attempting to simulate large molecular systems. Pages 89-114, Enrico Clementi... 

While quantum mechanical simulation of nuclear motion will become more practical in the future, classical mechanical molecular dynamics will remain an important tool for simulating large molecular systems for many years to come. Ab initio determination of forces will play an increasingly large role. But a system of N atoms requires at least 10 points to completely map out y(R) (ten points along each degree of freedom). For N of order 100, it is clearly prohibitive to comprehensively tabulate < y(R) in advance (in the absence of simplifications such as pairwise additivity). By contrast, a 1-ns trajectory with 1-fs time steps requires 10 evaluations of < y(R) and its derivatives, a very formidable task but far more accessible than the alternative. Thus, it will be essential in the future to develop on-the-fly methods for ab initio calculation of forces [4]. 

The rigorous Hartree-Fock method without approximations is too expensive to treat large systems such as large organic molecules. Thus semiempirical quantum chemistry methods, which are based on approximated Hartree-Fock formalism by inclusion of some parameters from empirical data, have been introduced to study systems that do not necessarily require the exact quantum solutions to understand the physicochemical properties and are, therefore, very important in simulating large molecular systems. 

The approach to the evaluation of vibrational spectra described above is based on classical simulations for which quantum corrections are possible. The incorporation of quantum effects directly in simulations of large molecular systems is one of the most challenging areas in theoretical chemistry today. The development of quantum simulation methods is particularly important in the area of molecular spectroscopy for which quantum effects can be important and where the goal is to use simulations to help understand the structural and dynamical origins of changes in spectral lineshapes with environmental variables such as the temperature. The direct evaluation of quantum time- correlation functions for anharmonic systems is extremely difficult. Our initial approach to the evaluation of finite temperature anharmonic effects on vibrational lineshapes is derived from the fact that the moments of the vibrational lineshape spectrum can be expressed as functions of expectation values of positional and momentum operators. These expectation values can be evaluated using extremely efficient quantum Monte-Carlo techniques. The main points are summarized below. 

The work described in this paper is an illustration of the potential to be derived from the availability of supercomputers for research in chemistry. The domain of application is the area of new materials which are expected to play a critical role in the future development of molecular electronic and optical devices for information storage and communication. Theoretical simulations of the type presented here lead to detailed understanding of the electronic structure and properties of these systems, information which at times is hard to extract from experimental data or from more approximate theoretical methods. It is clear that the methods of quantum chemistry have reached a point where they constitute tools of semi-quantitative accuracy and have predictive value. Further developments for quantitative accuracy are needed. They involve the application of methods describing electron correlation effects to large molecular systems. The need for supercomputer power to achieve this goal is even more acute. 

Despite advent of theoretical methods and techniques and faster computers, no single theoretical method seems to be capable of reliable computational studies of reactivities of biocatalysts. Ab initio quantum mechanical (QM) methods may be accurate but are still too expensive to apply to large systems like biocatalysts. Semi-empirical quantum methods are not as accurate but are faster, but may not be fast enough for long time simulation of large molecular systems. Molecular mechanics (MM) force field methods are not usually capable of dealing with bond-breaking and formation... 

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... 

Solvation plays a crucial role for the structure, dynamics and function of small molecules as well as for proteins and nucleic acids. When modeling solvation effects, especially for biomolecules, one often has to deal with large molecular systems and long timescales. Indeed, a proper account for solvation generally requires the inclusion of many solvent molecules, which leads to expanded system size and long simulation timescales required for capturing collective solvent response. 

Christen and van Gunsteren ° have developed a novel multiscale method that they call multigraining , which aims to use the CG model to enable both relaxation of large molecular systems and sampling of slow processes with concurrent atomic detail representation of the results. In this method, both an atomistic and a CG model of a molecule are used simultaneously. Each molecule in the simulation has... 

Direct dynamics is applicable to large molecular systems, but a lower level of electronic structure may be required as well as a blend of direct dynamics and analytic potential energy functions. This latter technique, often called quantum mechanical/molecular mechanical (QM/MM) direct dynamics [377], has been used to simulate SID unimolecular dynamics associated with protonated glycine ions, NH3CH2COOH [(gly-H)+j, colliding with a hydrogenated diamond 111 surface [378]. The potential energy for the system is represented by... 

---