Вычислительная химия: моделирование и применение

Branch of chemistry

Computational chemistry is a branch of chemistry that uses computer simulations to assist in solving chemical problems. It uses methods of theoretical chemistry incorporated into computer programs to calculate the structures and properties of molecules, groups of molecules, and solids. The importance of this subject stems from the fact that, with the exception of some relatively recent findings related to the hydrogen molecular ion (dihydrogen cation), achieving an accurate quantum mechanical depiction of chemical systems analytically, or in a closed form, is not feasible. The complexity inherent in the many body problem exacerbates the challenge of providing detailed descriptions of quantum mechanical systems. While computational results normally complement information obtained by chemical experiments, it can occasionally predict unobserved chemical phenomena.

There are several fields within computational chemistry. The prediction of the molecular structure of molecules by the use of the simulation of forces, or more accurate quantum chemical methods, to find stationary points on the energy surface as the position of the nuclei is varied. Storing and searching for data on chemical entities (see chemical databases). Identifying correlations between chemical structures and properties (see quantitative structure–property relationship (QSPR) and quantitative structure–activity relationship (QSAR)). Computational approaches to help in the efficient synthesis of compounds. Computational approaches to design molecules that interact in specific ways with other molecules (e. g. drug design and catalysis). These fields can give rise to several applications as shown below.

Computational chemistry is a tool for analyzing catalytic systems without doing experiments. Modern electronic structure theory and density functional theory has allowed researchers to discover and understand catalysts. Computational studies apply theoretical chemistry to catalysis research. Density functional theory methods calculate the energies and orbitals of molecules to give models of those structures. Using these methods, researchers can predict values like activation energy, site reactivity and other thermodynamic properties. Methods like density functional theory can be used to model drug molecules and find their properties, like their HOMO and LUMO energies and molecular orbitals. Computational chemists also help companies with developing informatics, infrastructure and designs of drugs. Aside from drug synthesis, drug carriers are also researched by computational chemists for nanomaterials. It allows researchers to simulate environments to test the effectiveness and stability of drug carriers. Understanding how water interacts with these nanomaterials ensures stability of the material in human bodies. These computational simulations help researchers optimize the material find the best way to structure these nanomaterials before making them.

How a computational method solves quantum equations impacts the accuracy and efficiency of the method. The split operator technique is one of these methods for solving differential equations. In computational chemistry, split operator technique reduces computational costs of simulating chemical systems. Computational costs are about how much time it takes for computers to calculate these chemical systems, as it can take days for more complex systems. Quantum systems are difficult and time consuming to solve for humans. Split operator methods help computers calculate these systems quickly by solving the sub problems in a quantum differential equation. The method does this by separating the differential equation into two different equations, like when there are more than two operators. Once solved, the split equations are combined into one equation again to give an easily calculable solution.

Semi empirical quantum chemistry methods are based on the Hartree–Fock method formalism, but make many approximations and obtain some parameters from empirical data. They were very important in computational chemistry from the 60s to the 90s, especially for treating large molecules where the full Hartree–Fock method without the approximations were too costly. The use of empirical parameters appears to allow some inclusion of correlation effects into the methods. Primitive semi empirical methods were designed even before, where the two electron part of the Hamiltonian is not explicitly included. For π electron systems, this was the Hückel method proposed by Erich Hückel, and for all valence electron systems, the extended Hückel method proposed by Roald Hoffmann. Sometimes, Hückel methods are referred to as "completely empirical" because they do not derive from a Hamiltonian. Yet, the term "empirical methods", or "empirical force fields" is usually used to describe molecular mechanics.

In many cases, large molecular systems can be modeled successfully while avoiding quantum mechanical calculations entirely. Molecular mechanics simulations, for example, use one classical expression for the energy of a compound, for instance, the harmonic oscillator. All constants appearing in the equations must be obtained beforehand from experimental data or ab initio calculations.

Molecular dynamics (MD) use either quantum mechanics, molecular mechanics or a mixture of both to calculate forces which are then used to solve Newton's laws of motion to examine the time dependent behavior of systems. The result of a molecular dynamics simulation is a trajectory that describes how the position and velocity of particles varies with time. The phase point of a system described by the positions and momenta of all its particles on a previous time point will determine the next phase point in time by integrating over Newton's laws of motion.

Monte Carlo (MC) generates configurations of a system by making random changes to the positions of its particles, together with their orientations and conformations where appropriate. It is a random sampling method, which makes use of the so called importance sampling. Importance sampling methods are able to generate low energy states, as this enables properties to be calculated accurately. The potential energy of each configuration of the system can be calculated, together with the values of other properties, from the positions of the atoms.

QM/MM is a hybrid method that attempts to combine the accuracy of quantum mechanics with the speed of molecular mechanics. It is useful for simulating very large molecules such as enzymes.

Quantum computational chemistry aims to exploit quantum computing to simulate chemical systems, distinguishing itself from the QM/MM (Quantum Mechanics/Molecular Mechanics) approach. While QM/MM uses a hybrid approach, combining quantum mechanics for a portion of the system with classical mechanics for the remainder, quantum computational chemistry exclusively uses quantum computing methods to represent and process information, such as Hamiltonian operators. Conventional computational chemistry methods often struggle with the complex quantum mechanical equations, particularly due to the exponential growth of a quantum system's wave function. Quantum computational chemistry addresses these challenges using quantum computing methods, such as qubitization and quantum phase estimation, which are believed to offer scalable solutions. Qubitization involves adapting the Hamiltonian operator for more efficient processing on quantum computers, enhancing the simulation's efficiency. Quantum phase estimation, on the other hand, assists in accurately determining energy eigenstates, which are critical for understanding the quantum system's behavior. While these techniques have advanced the field of computational chemistry, especially in the simulation of chemical systems, their practical application is currently limited mainly to smaller systems due to technological constraints. Nevertheless, these developments may lead to significant progress towards achieving more precise and resource efficient quantum chemistry simulations. In quantum chemistry, particularly, the complexity can grow exponentially with the number of electrons involved in the system. This exponential growth is a significant barrier to simulating large or complex systems accurately. Advanced algorithms in both fields strive to balance accuracy with computational efficiency. For instance, in MD, methods like Verlet integration or Beeman's algorithm are employed for their computational efficiency. In quantum chemistry, hybrid methods combining different computational approaches (like QM/MM) are increasingly used to tackle large biomolecular systems.

The following list illustrates the impact of computational complexity on algorithms used in chemical computations. It is important to note that while this list provides key examples, it is not comprehensive and serves as a guide to understanding how computational demands influence the selection of specific computational methods in chemistry.

Solves Newton's equations of motion for atoms and molecules.

The standard pairwise interaction calculation in MD leads to an complexity for particles. This is because each particle interacts with every other particle, resulting in interactions. Advanced algorithms, such as the Ewald summation or Fast Multipole Method, reduce this to or even by grouping distant particles and treating them as a single entity or using clever mathematical approximations.

Combines quantum mechanical calculations for a small region with molecular mechanics for the larger environment.

The complexity of QM/MM methods depends on both the size of the quantum region and the method used for quantum calculations. For example, if a Hartree Fock method is used for the quantum part, the complexity can be approximated as , where is the number of basis functions in the quantum region. This complexity arises from the need to solve a set of coupled equations iteratively until self consistency is achieved.

Finds a single Fock state that minimizes the energy.

NP hard or NP complete as demonstrated by embedding instances of the Ising model into Hartree Fock calculations. The Hartree Fock method involves solving the Roothaan Hall equations, which scales as to depending on implementation, with being the number of basis functions. The computational cost mainly comes from evaluating and transforming the two electron integrals. This proof of NP hardness or NP completeness comes from embedding problems like the Ising model into the Hartree Fock formalism.]]

Investigates the electronic structure or nuclear structure of many body systems such as atoms, molecules, and the condensed phases.

Traditional implementations of DFT typically scale as , mainly due to the need to diagonalize the Kohn Sham matrix. The diagonalization step, which finds the eigenvalues and eigenvectors of the matrix, contributes most to this scaling. Recent advances in DFT aim to reduce this complexity through various approximations and algorithmic improvements.

CCSD and CCSD(T) methods are advanced electronic structure techniques involving single, double, and in the case of CCSD(T), perturbative triple excitations for calculating electronic correlation effects.

Scales as where is the number of basis functions. This intense computational demand arises from the inclusion of single and double excitations in the electron correlation calculation. For other methods like MD or DFT, the computational complexity is often empirically observed and supported by algorithm analysis. In these cases, the proof of correctness is less about formal mathematical proofs and more about consistently observing the computational behaviour across various systems and implementations. Molecules consist of nuclei and electrons, so the methods of quantum mechanics apply. Computational chemists often attempt to solve the non relativistic Schrödinger equation, with relativistic corrections added, although some progress has been made in solving the fully relativistic Dirac equation. In principle, it is possible to solve the Schrödinger equation in either its time dependent or time independent form, as appropriate for the problem in hand; in practice, this is not possible except for very small systems. Therefore, a great number of approximate methods strive to achieve the best trade off between accuracy and computational cost. Accuracy can always be improved with greater computational cost. Significant errors can present themselves in ab initio models comprising many electrons, due to the computational cost of full relativistic inclusive methods. There is some dispute within the field whether or not the latter methods are sufficient to describe complex chemical reactions, such as those in biochemistry. Large molecules can be studied by semi empirical approximate methods. Even larger molecules are treated by classical mechanics methods that use what are called molecular mechanics (MM). In QM MM methods, small parts of large complexes are treated quantum mechanically (QM), and the remainder is treated approximately (MM).