Molecular modelling is a collective term that refers to theoretical methods and computational techniques to model or mimic the behaviour of
moleculeA molecule is defined as an electrically neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds. Molecules are distinguished from polyatomic ions in this strict sense...
s. The techniques are used in the fields of
computational chemistryComputational chemistry is a branch of chemistry that uses computers to assist in solving chemical problems. It uses the results of theoretical chemistry, incorporated into efficient computer programs, to calculate the structures and properties of molecules and solids...
,
computational biologyComputational biology is an interdisciplinary field that applies the techniques of computer science, applied mathematics and statistics to address biological problems. The main focus lies on developing mathematical modeling and computational simulation techniques...
and
materials scienceMaterials science or materials engineering is an interdisciplinary field involving the properties of matter and its applications to various areas of science and engineering. This science investigates the relationship between the structure of materials at atomic or molecular scales and their...
for studying 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.
Molecular modelling is a collective term that refers to theoretical methods and computational techniques to model or mimic the behaviour of
moleculeA molecule is defined as an electrically neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds. Molecules are distinguished from polyatomic ions in this strict sense...
s. The techniques are used in the fields of
computational chemistryComputational chemistry is a branch of chemistry that uses computers to assist in solving chemical problems. It uses the results of theoretical chemistry, incorporated into efficient computer programs, to calculate the structures and properties of molecules and solids...
,
computational biologyComputational biology is an interdisciplinary field that applies the techniques of computer science, applied mathematics and statistics to address biological problems. The main focus lies on developing mathematical modeling and computational simulation techniques...
and
materials scienceMaterials science or materials engineering is an interdisciplinary field involving the properties of matter and its applications to various areas of science and engineering. This science investigates the relationship between the structure of materials at atomic or molecular scales and their...
for studying 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 techniques is the atomistic level description of the molecular systems; the lowest level of information is individual atoms (or a small group of atoms). This is in contrast to
quantum chemistryQuantum chemistry is a branch of theoretical chemistry, which applies quantum mechanics and quantum field theory to address issues and problems in chemistry. The description of the electronic behavior of atoms and molecules as pertaining to their reactivity is one of the applications of quantum...
(also known as electronic structure calculations) where electrons are considered explicitly. The benefit of molecular modelling is that it reduces the complexity of the system, allowing many more particles (atoms) to be considered during simulations.
Molecular Mechanics
Molecular mechanicsMolecular mechanics uses Newtonian mechanics to model molecular systems. The potential energy of all systems in molecular mechanics is calculated using force fields...
is one aspect of molecular modelling, as it is refers to the use of
classical mechanicsIn the fields of physics, classical mechanics is one of the two major sub-fields of study in the science of mechanics, which is concerned with the set of physical laws governing and mathematically describing the motions of bodies and aggregates of bodies geometrically distributed within a certain...
/Newtonian mechanics to describe the physical basis behind the models. Molecular models typically describe atoms (nucleus and electrons collectively) as point charges with an associated mass. The interactions between neighbouring atoms are described by spring-like interactions (representing chemical bonds) and van der Waals forces. The
Lennard-Jones potentialThe Lennard-Jones potential is a mathematically simple model that describes the interaction between a pair of neutral atoms or molecules...
is commonly used to describe van der Waals forces. The electrostatic interactions are computed based on
Coulomb's lawCoulomb's law, sometimes called the Coulomb law, is an equation describing the electrostatic force between electric charges. It was studied and first published in the 1780s by French physicist Charles Augustin de Coulomb and was essential to the development of the theory of electromagnetism...
. Atoms are assigned coordinates in Cartesian space or in internal coordinates, and can also be assigned velocities in dynamical simulations. The atomic velocities are related to the temperature of the system, a macroscopic quantity. The collective mathematical expression is known as a
potential functionThe term potential function may refer to:* A mathematical function whose values are a physical potential.* The class of functions known as harmonic functions, which are the topic of study in potential theory....
and is related to the system internal energy (U), a thermodynamic quantity equal to the sum of potential and kinetic energies. Methods which minimize the potential energy are known as energy minimization techniques (e.g., steepest descent and conjugate gradient), while methods that model the behaviour of the system with propagation of time are known as
molecular dynamicsMolecular dynamics is a form of computer simulation in which atoms and molecules are allowed to interact for a period of time by approximations of known physics,...
.
This function, referred to as a
potential functionThe term potential function may refer to:* A mathematical function whose values are a physical potential.* The class of functions known as harmonic functions, which are the topic of study in potential theory....
, computes the molecular potential energy as a sum of energy terms that describe the deviation of bond lengths, bond angles and torsion angles away from equilibrium values, plus terms for non-bonded pairs of atoms describing van der Waals and electrostatic interactions. The set of parameters consisting of equilibrium bond lengths, bond angles, partial charge values, force constants and van der Waals parameters are collectively known as a
force fieldIn the context of molecular mechanics, a force field refers to the functional form and parameter sets used to describe the potential energy of a system of particles . Force field functions and parameter sets are derived from both experimental work and high-level quantum mechanical calculations...
. Different implementations of molecular mechanics use slightly different mathematical expressions, and therefore, different constants for the
potential functionThe term potential function may refer to:* A mathematical function whose values are a physical potential.* The class of functions known as harmonic functions, which are the topic of study in potential theory....
. The common force fields in use today have been developed by using high level quantum calculations and/or fitting to experimental data. The technique known as energy minimization is used to find positions of zero gradient for all atoms, in other words, a local energy minimum. Lower energy states are more stable and are commonly investigated because of their role in chemical and biological processes. A
molecular dynamicsMolecular dynamics is a form of computer simulation in which atoms and molecules are allowed to interact for a period of time by approximations of known physics,...
simulation, on the other hand, computes the behaviour of a system as a function of time. It involves solving Newton's laws of motion, principally the second law,
F = ma. Integration of Newton's laws of motion, using different integration algorithms, leads to atomic trajectories in space and time. The force on an atom is defined as the negative gradient of the potential energy function. The energy minimization technique is useful for obtaining a static picture for comparing between states of similar systems, while molecular dynamics provides information about the dynamic processes with the intrinsic inclusion of temperature effects.
Variables
Molecules can be modelled either in vacuum or in the presence of a solvent such as water. Simulations of systems in vacuum are referred to as
gas-phase simulations, while those that include the presence of solvent molecules are referred to as
explicit solvent simulations. In another type of simulation, the effect of solvent is estimated using an empirical mathematical expression; these are known as
implicit solvation simulations.
Applications
Molecular modelling methods are now routinely used to investigate the structure, dynamics and thermodynamics of inorganic, biological, and polymeric systems. The types of biological activity that have been investigated using molecular modelling include
protein foldingProtein folding is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
,
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
catalysisCatalysis is the process in which the rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. The catalyst may participate...
, protein stability, conformational changes associated with biomolecular function, and molecular recognition of proteins, DNA, and membrane complexes.
Popular software for molecular modelling
See also
External links