The term molecular mechanics refers to the use of Newtonian mechanics to model molecular systems. The potential energy of all systems in molecular mechanics is calculated using force fields. Molecular mechanics can be used to study small molecules as well as large biological systems or material assemblies with many thousands to millions of atoms. Classical mechanics is a branch of physics which studies the deterministic motion of objects. ... In science, a molecule is the smallest particle of a pure chemical substance that still retains its chemical composition and properties. ... It has been suggested that this article or section be merged with force field (physics). ...

All-atomistic molecular mechanics methods have the following properties:

• Each atom is simulated as a single particle
• Each particle is assigned a radius (typically the van der Waals radius), polarizability, and a constant net charge (generally derived from quantum calculations and/or experiment)
• Bonded interactions are treated as "springs" with an equilibrium distance equal to the experimental or calculated bond length

Variations on this theme are possible; for example, many simulations have historically used a "united-atom" representation in which methyl and methylene groups were represented as a single particle, and large protein systems are commonly simulated using a "bead" model that assigns two to four particles per amino acid. The van der Waals radius of an atom is the radius of an imaginary hard sphere which can be used to model the atom for many purposes. ... In chemistry a methyl-group is a hydrophobic Alkyl functional group which is derived from methane (CH4). ... In chemistry, methylene is a divalent functional group CH2 derived formally from methane. ... The general structure of an α-amino acid molecule, with the amine group on the left and the carboxyl group on the right. ...

Functional Form

The following functional abstraction, known as a potential function or force field in Chemistry, calculates the system's potential energy in a given conformation as a sum of individual energy terms. It has been suggested that this article or section be merged with force field (physics). ...

The exact functional form of the potential function depends on the particular simulation program being used. Generally the bond and angle terms are modeled as harmonic potentials centered around equilibrium values derived from experiment or theoretical calculations of electronic structure performed with software like Gaussian. For accurate reproduction of vibrational spectra, the Morse potential can be used instead, at computational cost. The dihedral or torsional terms typically have multiple minima and thus cannot be modeled as harmonic oscillators, though their specific functional form varies with the implementation. This class of terms may include "improper" dihedral terms, which function as correction factors for out-of-plane deviations (for example, they can be used to keep benzene rings planar). In classical mechanics, a Harmonic oscillator is a system which, when displaced from its equilibrium position, experiences a restoring force proportional to the displacement according to Hookes law: where is a positive constant. ... Generally, the word gaussian pertains to Carl Friedrich Gauss and his ideas. ... The Morse potential, named after physicist Philip M. Morse, is a convenient model for the potential energy of a diatomic molecule. ... Benzene, also known as benzol, is an organic chemical compound with the formula C6H6. ...

The non-bonded terms are much more computationally costly to calculate in full, since a typical atom is bonded to only a few of its neighbors, but interacts with every other atom in the simulation. Fortunately the van der Waals term falls off rapidly - it is typically modeled using a "6-12 Lennard-Jones potential", which means that attractive forces fall off with distance as r^-6 and repulsive forces as r^-12, where r represents the distance between two atoms. Generally a cutoff radius is used so that atom pairs whose distances is greater than the cutoff have a van der Waals interaction energy of zero. Johannes Diderik van der Waals, a 1910 Nobel Prize winner, was responsible for a number of advances in physical chemistry which are named after him. ... Neutral atoms and molecules are subject to two distinct forces in the limit of large distance, and short distance: an attractive van der Waals force, or dispersion force, at long ranges, and a repulsion force, the result of overlapping electron orbitals, referred to as Pauli repulsion (from Pauli exclusion principle). ...

The electrostatic terms are notoriously difficult to calculate well because they do not fall off rapidly with distance, and long-range electrostatic interactions are often important features of the system under study (especially for proteins). The basic functional form is the Coulomb potential, which only falls off as r^-1. A variety of methods are used to address this problem, the simplest being a cutoff radius similar to that used for the van der Waals terms. However, this introduces a sharp discontinuity between atoms inside and atoms outside the radius. Switching or scaling functions that modulate the apparent electrostatic energy are somewhat more accurate methods that multiply the calculated energy by a smoothly varying scaling factor from 0 to 1 at the outer and inner cutoff radii. Other more sophisticated but computationally intensive methods are known as particle mesh Ewald (PME) and the multipole algorithm. A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Coulombs torsion balance In physics, Coulombs law is an inverse-square law indicating the magnitude and direction of electrostatic force that one stationary, electrically charged object of small dimensions (ideally, a point source) exerts on another. ...

In addition to the functional forms of each energy term, a useful energy function must also include parameters for force constants, van der Waals multipliers, and other constant terms. These terms, together with the equilibrium bond, angle, and dihedral values, partial charge values, atomic masses and radii, and energy function definitions, are collectively known as a force field. Parameterization is typically done through agreement with experimental values and theoretical calculations results. Each force field is parameterized to be internally consistent, but the parameters are generally not transferable from one force field to another. It has been suggested that this article or section be merged with force field (physics). ...

Areas of application

The prototypical Molecular Mechanics application is energy minimization. That is, the force field is used as an optimization criterion and the (local) minimum searched by an appropriate algorithm (e.g. steepest descent). Global energy optimization can be accomplished using simulated annealing, the Metropolis algorithm and other Monte Carlo methods, or using different deterministic methods of discrete or continuous optimization. The main aim of optimization methods is finding the lowest energy conformation of a molecule or identifying a set of low-energy conformers that are in equilibrium with each other. The force field represents only the enthalpic component of free energy, and only this component is included during energy minimization. However, the analysis of equlibrium between different states requires also conformational entropy be included, which is possible but rarely done. It has been suggested that this article or section be merged with force field (physics). ... In mathematics, the term optimization refers to the study of problems that have the form Given: a function f : A R from some set A to the real numbers Sought: an element x0 in A such that f(x0) ≤ f(x) for all x in A (minimization) or such that... Gradient descent is an optimization algorithm that approaches a local minimum of a function by taking steps proportional to the negative of the gradient (or the approximate gradient) of the function at the current point. ... Simulated annealing (SA) is a generic probabilistic meta-algorithm for the global optimization problem, namely locating a good approximation to the global optimum of a given function in a large search space. ... The Proposal distribution Q proposes the next point that the random walk might move to. ... Monte Carlo methods are a widely used class of computational algorithms for simulating the behavior of various physical and mathematical systems. ... In thermodynamics, the enthalpy is a thermodynamic potential which measures the useful work obtainable from a closed thermodynamic system at a constant pressure. ... In thermodynamics, the Gibbs free energy is a thermodynamic potential which measures the useful work obtainable from a closed thermodynamic system at a constant temperature and pressure. ... Conformational entropy is the entropy associated with the physical arrangement of a polymer chain that assumes a compact or globular state in solution. ...

Other applications of MM include potential energy mapping and ligand docking simulations. Computational molecular docking is a research technique for predicting whether one molecule will bind to another, usually a protein. ...

Molecular Mechanics and Molecular Dynamics (MD) are related but different. Main purpose of MD is modeling of molecular motions, although it is also applied for optimization, for example using simulated annealing. MM implements more "static" energy minimization methods to study the potential energy surfaces of different molecular systems. However, MM can also provide important dynamic parameters, such as energy barriers between different conformers or steepness of a potential energy surface around a local minumum. MD and MM are usually based on the same classical force fields. But MD may be also based on quantum chemical methods like DFT. MM is also loosely used to define a set of techniques in molecular modeling. Molecular dynamics (MD) simulation is a special discipline of molecular modelling. ... Simulated annealing (SA) is a generic probabilistic meta-algorithm for the global optimization problem, namely locating a good approximation to the global optimum of a given function in a large search space. ... It has been suggested that this article or section be merged with force field (physics). ... Linus Pauling, as a pioneer of the valence bond theory, is one of the first quantum chemists. ... Density functional theory (DFT) is a quantum mechanical method used in physics and chemistry to investigate the electronic structure of many-body systems, in particular molecules and the condensed phases. ... Molecular modelling is a collection of techniques to model or mimic the behaviour of molecules. ...

Environment and Solvation

There are several ways of defining the environment surrounding the molecule or molecules of interest in molecular mechanics. A system can be simulated in vacuum (known as a gas-phase simulation) with no surrounding environment at all, but this is usually not desirable because it introduces artifacts in the molecular geometry, especially in charged molecules. Surface charges that would ordinarily interact with solvent molecules instead interact with each other, producing molecular conformations that are unlikely to be present in any other environment. The "best" way to solvate a system is to place explicit water molecules in the simulation box with the molecules of interest and treat the water molecules as interacting particles like those in the molecule. A variety of water models exist with increasing levels of complexity, representing water as a simple hard sphere (a united-atom approach), as three separate particles with fixed bond angles, or even as four or five separate interaction centers to account for unpaired electrons on the oxygen atom. Unsurprisingly, the more complex the water model, the more computationally intensive the simulation. A compromise approach has been found in implicit solvation, which replaces the explicitly represented water molecules with a mathematical expression that reproduces the average behavior of water molecules (or other solvents such as lipids). This method is useful for preventing artifacts that arise from vacuum simulations and reproduces bulk solvent properties well, but cannot reproduce situations in which individual water molecules have interesting interactions with the molecules under study. Implicit solvation (sometimes known as continuum solvation) is a method of representing solvent in molecular dynamics simulations and molecular mechanics (e. ...

Software Packages

Limited list; many more are available

• AMBER
• CHARMM
• Ghemical
• GROMOS
• GROMACS
• GULP
• NAMD
• STR3DI32
• TINKER
• QUANTUM 3.2
• Atomsmith

Amber pendants. ... CHARMM (Chemistry at HARvard Macromolecular Mechanics) is a force field for molecular dynamics as well as the name for the molecular dynamics simulation package associated with this force field. ... Ghemical is a computational chemistry software package written in C++ and released under the GNU GPL. The program has GUI based on GTK+2 and supports quantum mechanical and molecular mechanic models, with geometry optimization, molecular dynamics, and a large set of visualization tools. ... GROMOS is a force field for molecular dynamics developed at the University of Groningen and the ETH Zurich. ... GROMACS (Groningen Machine for Chemical Simulations) is a molecular dynamics simulation package developed in the University of Groningen. ... NAMD is an open-source molecular dynamics simulation package developed in the University of Illinois. ... STR3DI32 STR3DI32 (an acronym for STRuctures in 3 DImensions) is a modern Molecular Mechanics (MM) based molecular modeling program that was developed by Vernon G. S. Box (an organic chemistry professor at the City College, City University of New York). ...

See also

Force field in Chemistry It has been suggested that this article or section be merged with force field (physics). ...

References

• U. Burkert and N.L. Allinger, Molecular Mechanics, 1982, ISBN 0-8412-0885-9
• Vernon G. S. Box, The Molecular Mechanics of Quantized Valence Bonds, J. Mol. Model., 3, 124, 1997
• Vernon G. S. Box, The anomeric effect of monosaccharides and their derivatives. Insights from the new QVBMM molecular mechanics force field, Heterocycles, 48, 2389 1998
• Vernon G. S. Box, Stereo-electronic effects in polynucleotides and their double helices, J. Mol. Struct., 689, 33-41 2004
• O. Becker, A.D. MacKerell, Jr., B. Roux and M. Watanabe, Editors, Computational Biochemistry and Biophysics, Marcel Dekker Inc., New York, 2001, ISBN 0-8247-0455-X
• MacKerell, A.D., Jr., Empirical Force Fields for Biological Macromolecules: Overview and Issues, Journal of Computational Chemistry, 25: 1584-1604, 2004
• Schlick, T. Molecular Modeling and Simulation: An Interdisciplinary Guide. Springer-Verlag, New York, NY: 2002. ISBN 0-387-95404-X.