Computational chemistry is a branch of chemistry that uses computer simulation 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. It is essential because, apart from relatively recent results concerning the hydrogen molecular ion, the quantum many-body problem cannot be solved analytically, much less in closed form. While computational results normally complement the information obtained by chemical experiments, it can in some cases predict hitherto unobserved chemical phenomena. It is widely used in the design of new drugs and materials.
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.
An ion source is a device that creates atomic and molecular ions. Ion sources are used to form ions for mass spectrometers, optical emission spectrometers, particle accelerators, ion implanters and ion engines.
A solvation shell or solvation sheath is the solvent interface of any chemical compound or biomolecule that constitutes the solute in a solution. When the solvent is water it is called a hydration shell or hydration sphere. The number of solvent molecules surrounding each unit of solute is called the hydration number of the solute.
Molecular mechanics uses classical mechanics to model molecular systems. The Born–Oppenheimer approximation is assumed valid and the potential energy of all systems is calculated as a function of the nuclear coordinates using force fields. Molecular mechanics can be used to study molecule systems ranging in size and complexity from small to large biological systems or material assemblies with many thousands to millions of atoms.
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 and molecular modelling, a force field is a computational method that is used to estimate the forces between atoms within molecules and also between molecules. More precisely, the force field refers to the functional form and parameter sets used to calculate the potential energy of a system of atoms or coarse-grained particles in molecular mechanics, molecular dynamics, or Monte Carlo simulations. The parameters for a chosen energy function may be derived from experiments in physics and chemistry, calculations in quantum mechanics, or both. Force fields are interatomic potentials and utilize the same concept as force fields in classical physics, with the difference that the force field parameters in chemistry describe the energy landscape, from which 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.
In computational biology, protein pKa calculations are used to estimate the pKa values of amino acids as they exist within proteins. These calculations complement the pKa values reported for amino acids in their free state, and are used frequently within the fields of molecular modeling, structural bioinformatics, and computational biology.
Frederic Middlebrook Richards, commonly referred to as Fred Richards, was an American biochemist and biophysicist known for solving the pioneering crystal structure of the ribonuclease S enzyme in 1967 and for defining the concept of solvent-accessible surface. He contributed many key experimental and theoretical results and developed new methods, garnering over 20,000 journal citations in several quite distinct research areas. In addition to the protein crystallography and biochemistry of ribonuclease S, these included solvent accessibility and internal packing of proteins, the first side-chain rotamer library, high-pressure crystallography, new types of chemical tags such as biotin/avidin, the nuclear magnetic resonance (NMR) chemical shift index, and structural and biophysical characterization of the effects of mutations.
Hydrophobic collapse is a proposed process for the production of the 3-D conformation adopted by polypeptides and other molecules in polar solvents. The theory states that the nascent polypeptide forms initial secondary structure creating localized regions of predominantly hydrophobic residues. The polypeptide interacts with water, thus placing thermodynamic pressures on these regions which then aggregate or "collapse" into a tertiary conformation with a hydrophobic core. Incidentally, polar residues interact favourably with water, thus the solvent-facing surface of the peptide is usually composed of predominantly hydrophilic regions.
Implicit solvation is a method to represent solvent as a continuous medium instead of individual “explicit” solvent molecules, most often used in molecular dynamics simulations and in other applications of molecular mechanics. The method is often applied to estimate free energy of solute-solvent interactions in structural and chemical processes, such as folding or conformational transitions of proteins, DNA, RNA, and polysaccharides, association of biological macromolecules with ligands, or transport of drugs across biological membranes.
COSMO is a calculation method for determining the electrostatic interaction of a molecule with a solvent. COSMO is a dielectric continuum model. These models can be used in computational chemistry to model solvation effects. COSMO has become a popular method of these solvation models in recent years. The COSMO formalism is similar to the method proposed earlier by Hoshi et al. The COSMO approach is based - as many other dielectric continuum models - on the surface segmentation of a molecule surface.
In molecular modelling, docking is a method which predicts the preferred orientation of one molecule to another when bound together in a stable complex. In the case of protein docking, the search space consists of all possible orientations of the protein with respect to the ligand. Flexible docking in addition considers all possible conformations of the protein paired with all possible conformations of the ligand.
Hydrophobicity scales are values that define the relative hydrophobicity or hydrophilicity of amino acid residues. The more positive the value, the more hydrophobic are the amino acids located in that region of the protein. These scales are commonly used to predict the transmembrane alpha-helices of membrane proteins. When consecutively measuring amino acids of a protein, changes in value indicate attraction of specific protein regions towards the hydrophobic region inside lipid bilayer.
FoldX is a protein design algorithm that uses an empirical force field. It can determine the energetic effect of point mutations as well as the interaction energy of protein complexes. FoldX can mutate protein and DNA side chains using a probability-based rotamer library, while exploring alternative conformations of the surrounding side chains.
Residue depth (RD) is a solvent exposure measure that describes to what extent a residue is buried in the protein structure space. It complements the information provided by conventional accessible surface area (ASA).
Computer Atlas of Surface Topography of Proteins (CASTp) aims to provide comprehensive and detailed quantitative characterization of topographic features of protein, is now updated to version 3.0. Since its release in 2006, the CASTp server has ≈45000 visits and fulfills ≈33000 calculation requests annually. CASTp has been proven as a confident tool for a wide range of researches, including investigations of signaling receptors, discoveries of cancer therapeutics, understanding of mechanism of drug actions, studies of immune disorder diseases, analysis of protein–nanoparticle interactions, inference of protein functions and development of high-throughput computational tools. This server is maintained by Jie Liang's lab in University of Illinois at Chicago.
Volume, Area, Dihedral Angle Reporter (VADAR) is a freely available protein structure validation web server that was developed as a collaboration between Dr. Brian Sykes and Dr. David Wishart at the University of Alberta. VADAR consists of over 15 different algorithms and programs for assessing and validating peptide and protein structures from their PDB coordinate data. VADAR is capable of determining secondary structure, identifying and classifying six different types of beta turns, determining and calculating the strength of C=O -- N-H hydrogen bonds, calculating residue-specific accessible surface areas (ASA), calculating residue volumes, determining backbone and side chain torsion angles, assessing local structure quality, evaluating global structure quality, and identifying residue "outliers". The results have been validated through extensive comparison to published data and careful visual inspection. VADAR produces both text and graphical output with most of the quantitative data presented in easily viewed tables. In particular, VADAR's output is presented in a vertical, tabular format with most of the sequence data, residue numbering and any other calculated property or feature presented from top to bottom, rather than from left to right.
Relative accessible surface area or relative solvent accessibility (RSA) of a protein residue is a measure of residue solvent exposure. It can be calculated by formula:
