Force Fields for Biomolecules

Modifications of the various versions of the AMBER parameter sets are implemented in numerous commercial and academic software packages. They are often referred to as AMBER. In every case, the user should read the documentation provided critically, and check the implementation by comparing the results of the implementation with original data. 

The Empirical Conformational Energy Program for Peptides, ECEPP [63, 64], is one of the first empirical interatomic potentials whose derivation is based both on gas-phase and X-ray crystal data [65], It was developed in 1975 and updated in 1983 and 1992. The actual distribution (dated May, 2000) can be downloaded without charge for academic use. 

Spedal emphasis was placed on the calculation of spectroscopic properties and properties of distorted molecules. The potential energy function of CFF is domi- 

Inadequate availability of experimental data can considerably inhibit the development of improved energy functions for more accurate simulations of energetic, structural, and spectroscopic properties. This has led to the development of class II force fields such as CFF and the Merck Molecular Force Field (MMFF), which are both based primarily on quantum mechanical calculations of the energy surface. The purpose of MMFF, which has been developed by Thomas Halgren at Merck and Co., is to be able to handle all functional groups of interest in pharmaceutical design. 

Chipot, A. PohorUle, The development/application of a minimalisf organic/biochemical molecular mechanic force field using a combination of ab-initio calculations and experimental data, in Computer Simulation of Biomolecular Systems. 

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MD simulations of lipid bilayers as a function of temperature have not been extensive. The reliability of force fields is dependent on the accuracy of describing the torsional potential energies of alkanes which prompted improvements of some of the most commonly applied force fields for biomolecules [125] using recent ab initio computations of torsional potential in various trans/gauche n-alkanes (up to -decane) [126]. A few recent MD simulations have analyzed the temperature effects on models of PC lipid bUayers, mainly for long chains (16-18 C), with a reasonably successful prediction of the phase transition temperamre (error of 12-50 °C) [106, 127-130]. These studies relate the melting temperamre to the fast increase of gauche conformers in the alkyl chains. 

Popular force fields for simulations on organic and biomolecules include the following ... 

Polarization of the MM environment by the QM region is usually not included, because MM protein force fields do not as yet allow for polarization, or indeed any changes in atomic charges. QM/MM methods which include polarization of the MM system have been developed for small systems.106 QM/MM calculations should help in developing polarizable MM force fields for example, in investigating polarization effects for small (QM) regions in large biomolecules.107... 

Assisted Model Building with Energy Refinement refers to a MM force field for the simulation of biomolecules and a package of molecular simulation programs. 

Some force fields for MM calculations on biomolecules (for example, OPLS, AMBER, CHARMM) exist in both united-atom (UA) and all-atom (AA) versions. A UA force field saves computational time by not explicitly including hydrogen atoms bonded to aliphatic carbon atoms. Instead, the field contains parameters for the CHj, CH2, and CH groups. 

Solvents (especially water) play a critical role in many biological processes or chemical reactions, so the development and improvement of coarse-grained force fields for solvents are essential to the CG modeling of biomolecules in solution. In addition, these small... 

The most basic approach to carry out MD simulations for larger systems is to use classical force fields. A variety of different force fields for molecular mechanics (MM) simulations has been developed,which are mainly intended to describe the non-reactive dynamics of large systems. In particular in the field of biochemistry force fields play an essential role to study the complex properties of large biomolecules. However, classical force fields require the specification of the connectivity of the atoms. Therefore, they are not able to describe chemical reactions, i.e., the making and breaking of bonds. To describe reactions, they can be combined with quantum mechanical (QM) methods in so-called QM/MM simulations. In recent years also reactive force fields , e.g. ReaxFF, have been introduced, which overcome this limitation. However, these reactive force fields are typically highly adapted to specific systems by analytic terms customized to describe e.g. certain bonding situations, and only a few applications have been reported so far. 

Current research in water potentials tends to focus on incorporating explicit many-body polarization terms in the water-water energy. This avoids the pairwise additive approach, i.e., the effective media approximation inherent in pairwise additive water potentials, and allows for a better parameterization of the true water-water interaction. Two main avenues for treating polarization effects have developed in the last decade an explicit treatment of classical polarization and fluctuating charge models. The effort expended to find suitable water models will slowly pay off in an enhanced awareness of how to improve current molecular force fields for interactions of other types (e.g., between organic solutes, biomolecules, etc.). 

The molecular mechanics force fields available include MM+, OPLS, BIO+, and AMBER. Parameters missing from the force field will be automatically estimated. The user has some control over cutoff distances for various terms in the energy expression. Solvent molecules can be included along with periodic boundary conditions. The molecular mechanics calculations tested ran without difficulties. Biomolecule computational abilities are aided by functions for superimposing molecules, conformation searching, and QSAR descriptor calculation. 

Focuses on force field calculations for understanding the dynamic properties of proteins and nucleic acids. Provides a useful introduction to several computational techniques, including molecular mechanics minimization and molecular dynamics. Includes discussions of research involving structural changes and short time scale dynamics of these biomolecules, and the influence of solvent in these processes. 

United atom force fields (see United versus All Atom Force Fields on page 28) are sometimes used for biomolecules to decrease the number of nonbonded interactions and the computation time. Another reason for using a simplified potential is to reduce the dimensionality of the potential energy surface. This, in turn, allows for more samples of the surface. 

Empirical energy functions can fulfill the demands required by computational studies of biochemical and biophysical systems. The mathematical equations in empirical energy functions include relatively simple terms to describe the physical interactions that dictate the structure and dynamic properties of biological molecules. In addition, empirical force fields use atomistic models, in which atoms are the smallest particles in the system rather than the electrons and nuclei used in quantum mechanics. These two simplifications allow for the computational speed required to perform the required number of energy calculations on biomolecules in their environments to be attained, and, more important, via the use of properly optimized parameters in the mathematical models the required chemical accuracy can be achieved. The use of empirical energy functions was initially applied to small organic molecules, where it was referred to as molecular mechanics [4], and more recently to biological systems [2,3]. 

Listed is a collection of general-purpose molecular dynamics computer simulation packages for the study of molecular systems. The packages include a wide variety of functionalities for the analysis and simulation of biomolecules. In addition, they contain integrated force fields. 

Amadasi, A., Spyrakis, E., Cozzini, P., Abraham, D.)., Kellogg, G. E Mozzarelli, A. Mapping the energetics of water-protein and water-ligand interactions with the natural HINT force field predictive tools for characterizing the roles of water in biomolecules. J. Mol. Biol. 2006, 358, 289-309. 

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