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, 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.
Theoretical chemistry is the branch of chemistry which develops theoretical generalizations that are part of the theoretical arsenal of modern chemistry: for example, the concepts of chemical bonding, chemical reaction, valence, the surface of potential energy, molecular orbitals, orbital interactions, and molecule activation.
Molecular dynamics (MD) is a computer simulation method for analyzing the physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamic "evolution" of the system. In the most common version, the trajectories of atoms and molecules are determined by numerically solving Newton's equations of motion for a system of interacting particles, where forces between the particles and their potential energies are often calculated using interatomic potentials or molecular mechanical force fields. The method is applied mostly in chemical physics, materials science, and biophysics.
Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Drug design frequently but not necessarily relies on computer modeling techniques. This type of modeling is sometimes referred to as computer-aided drug design. Finally, drug design that relies on the knowledge of the three-dimensional structure of the biomolecular target is known as structure-based drug design. In addition to small molecules, biopharmaceuticals including peptides and especially therapeutic antibodies are an increasingly important class of drugs and computational methods for improving the affinity, selectivity, and stability of these protein-based therapeutics have also been developed.
Molecular modelling encompasses all methods, theoretical and computational, used to model or mimic the behaviour of molecules. The methods are used in the fields of computational chemistry, drug design, computational biology and materials science to study molecular systems ranging from small chemical systems to large biological molecules and material assemblies. The simplest calculations can be performed by hand, but inevitably computers are required to perform molecular modelling of any reasonably sized system. The common feature of molecular modelling methods is the atomistic level description of the molecular systems. This may include treating atoms as the smallest individual unit, or explicitly modelling protons and neutrons with its quarks, anti-quarks and gluons and electrons with its photons.
In the field of molecular modeling, docking is a method which predicts the preferred orientation of one molecule to a second when a ligand and a target are bound to each other to form a stable complex. Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules using, for example, scoring functions.
In the context of chemistry, molecular physics, physical chemistry, and molecular modelling, a force field is a computational model that is used to describe the forces between atoms within molecules or between molecules as well as in crystals. Force fields are a variety of interatomic potentials. More precisely, the force field refers to the functional form and parameter sets used to calculate the potential energy of a system on the atomistic level. Force fields are usually used in molecular dynamics or Monte Carlo simulations. The parameters for a chosen energy function may be derived from classical laboratory experiment data, calculations in quantum mechanics, or both. Force fields utilize the same concept as force fields in classical physics, with the main difference being that the force field parameters in chemistry describe the energy landscape on the atomistic level. From a force field, the acting forces on every particle are derived as a gradient of the potential energy with respect to the particle coordinates.
Spartan is a molecular modelling and computational chemistry application from Wavefunction. It contains code for molecular mechanics, semi-empirical methods, ab initio models, density functional models, post-Hartree–Fock models, and thermochemical recipes including G3(MP2) and T1. Quantum chemistry calculations in Spartan are powered by Q-Chem.
Protein–ligand docking is a molecular modelling technique. The goal of protein–ligand docking is to predict the position and orientation of a ligand when it is bound to a protein receptor or enzyme. Pharmaceutical research employs docking techniques for a variety of purposes, most notably in the virtual screening of large databases of available chemicals in order to select likely drug candidates. There has been rapid development in computational ability to determine protein structure with programs such as AlphaFold, and the demand for the corresponding protein-ligand docking predictions is driving implementation of software that can find accurate models. Once the protein folding can be predicted accurately along with how the ligands of various structures will bind to the protein, the ability for drug development to progress at a much faster rate becomes possible.
Tinker, previously stylized as TINKER, is a suite of computer software applications for molecular dynamics simulation. The codes provide a complete and general set of tools for molecular mechanics and molecular dynamics, with some special features for biomolecules. The core of the software is a modular set of callable routines which allow manipulating coordinates and evaluating potential energy and derivatives via straightforward means.
Free-energy perturbation (FEP) is a method based on statistical mechanics that is used in computational chemistry for computing free-energy differences from molecular dynamics or Metropolis Monte Carlo simulations.
Journal of Chemical Theory and Computation is a peer-reviewed scientific journal, established in 2005 by the American Chemical Society. It is indexed in Chemical Abstracts Service (CAS), Scopus, British Library, and Web of Science. The current editor-in-chief is Laura Gagliardi. Currently as of the year 2022, JCTC has 18 volumes.
Biochemical and Organic Simulation System (BOSS) is a general-purpose molecular modeling program that performs molecular mechanics calculations, Metropolis Monte Carlo statistical mechanics simulations, and semiempirical Austin Model 1 (AM1), PM3, and PDDG/PM3 quantum mechanics calculations. The molecular mechanics calculations cover energy minimizations, normal mode analysis and conformational searching with the Optimized Potentials for Liquid Simulations (OPLS) force fields. BOSS is developed by Prof. William L. Jorgensen at Yale University, and distributed commercially by Cemcomco, LLC and Schrödinger, Inc.
Donald Gene Truhlar is an American scientist working in theoretical and computational chemistry and chemical physics with special emphases on quantum mechanics and chemical dynamics.
Sharon Hammes-Schiffer is a physical chemist who has contributed to theoretical and computational chemistry. She is currently the A. Barton Hepburn Professor of Chemistry at Princeton University. She has served as senior editor and deputy editor of the Journal of Physical Chemistry and advisory editor for Theoretical Chemistry Accounts. She is the editor-in-chief of Chemical Reviews.
Kenneth M. Merz Jr. is an American biochemist and molecular biologist currently the Joseph Zichis Chair and a distinguished university professor at Michigan State University and editor-in-chief of American Chemical Society's Journal of Chemical Information and Modeling. A highly cited expert in his field, his research interests are in computational chemistry and biology and computer-aided drug design (CADD). His group has been involved in developing the widely using AMBER suite of programs for simulating chemical and biological systems and the QUICK program for quantum chemical calculations.
Dr. Dan Thomas Major is a Professor of Chemistry at Bar Ilan University specializing in Computational Chemistry.
Marcin Maciej Hoffmann is a Polish scientist and entrepreneur. He is a professor of chemistry at the Faculty of Chemistry of Adam Mickiewicz University in Poznań.
Charles David Sherrill is a professor of chemistry and computational science and engineering at Georgia Tech working in the areas of theoretical chemistry, computational quantum chemistry, and scientific computing. His research focuses on the development and application of theoretical methods for non-covalent interactions between molecules. He is the lead principal investigator of the Psi open-source quantum chemistry program.
