We describe the development, current features, and some directions for future development of the Amber package of computer programs. This package evolved from a program that was constructed in the late 1970s to do Assisted Model Building with Energy Refinement, and now contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates.

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The Amber biomolecular simulation programs

Recent advances in hardware and software have enabled increasingly long molecular dynamics (MD) simulations of biomolecules, exposing certain limitations in the accuracy of the force fields used for such simulations and spurring efforts to refine these force fields. Recent modifications to the Amber and CHARMM protein force fields, for example, have improved the backbone torsion potentials, remedying deficiencies in earlier versions. Here, we further advance simulation accuracy by improving the amino acid side-chain torsion potentials of the Amber ff99SB force field. First, we used simulations of model alpha-helical systems to identify the four residue types whose rotamer distribution differed the most from expectations based on Protein Data Bank statistics. Second, we optimized the side-chain torsion potentials of these residues to match new, high-level quantum-mechanical calculations. Finally, we used microsecond-timescale MD simulations in explicit solvent to validate the resulting force field against a large set of experimental NMR measurements that directly probe side-chain conformations. The new force field, which we have termed Amber ff99SB-ILDN, exhibits considerably better agreement with the NMR data. Proteins 2010. © 2010 Wiley-Liss, Inc.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/prot.22711

Improved side‐chain torsion potentials for the Amber ff99SB protein force field

A potential model intended to be a general purpose model for the condensed phases of water is presented. TIP4P/2005 is a rigid four site model which consists of three fixed point charges and one Lennard-Jones center. The parametrization has been based on a fit of the temperature of maximum density (indirectly estimated from the melting point of hexagonal ice), the stability of several ice polymorphs and other commonly used target quantities. The calculated properties include a variety of thermodynamic properties of the liquid and solid phases, the phase diagram involving condensed phases, properties at melting and vaporization, dielectric constant, pair distribution function, and self-diffusion coefficient. These properties cover a temperature range from 123to573K and pressures up to 40000bar. The model gives an impressive performance for this variety of properties and thermodynamic conditions. For example, it gives excellent predictions for the densities at 1bar with a maximum density at 278K and an aver...

http://cacharro.quim.ucm.es/publicaciones/JCP_123_234505_2005.pdf

A general purpose model for the condensed phases of water: TIP4P/2005

Alkali (Li+, Na+, K+, Rb+, and Cs+) and halide (F−, Cl−, Br−, and I−) ions play an important role in many biological phenomena, roles that range from stabilization of biomolecular structure, to influence on biomolecular dynamics, to key physiological influence on homeostasis and signaling. To properly model ionic interaction and stability in atomistic simulations of biomolecular structure, dynamics, folding, catalysis, and function, an accurate model or representation of the monovalent ions is critically necessary. A good model needs to simultaneously reproduce many properties of ions, including their structure, dynamics, solvation, and moreover both the interactions of these ions with each other in the crystal and in solution and the interactions of ions with other molecules. At present, the best force fields for biomolecules employ a simple additive, nonpolarizable, and pairwise potential for atomic interaction. In this work, we describe our efforts to build better models of the monovalent ions within t...

Determination of Alkali and Halide Monovalent Ion Parameters for Use in Explicitly Solvated Biomolecular Simulations

Molecular dynamics (MD) allows the study of biological and chemical systems at the atomistic level on timescales from femtoseconds to milliseconds. It complements experiment while also offering a way to follow processes difficult to discern with experimental techniques. Numerous software packages exist for conducting MD simulations of which one of the widest used is termed Amber. Here, we outline the most recent developments, since version 9 was released in April 2006, of the Amber and AmberTools MD software packages, referred to here as simply the Amber package. The latest release represents six years of continued development, since version 9, by multiple research groups and the culmination of over 33 years of work beginning with the first version in 1979. The latest release of the Amber package, version 12 released in April 2012, includes a substantial number of important developments in both the scientific and computer science arenas. We present here a condensed vision of what Amber currently supports and where things are likely to head over the coming years. Figure 1 shows the performance in ns/day of the Amber package version 12 on a single-core AMD FX-8120 8-Core 3.6GHz CPU, the Cray XT5 system, and a single GPU GTX680. © 2012 John Wiley & Sons, Ltd.

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An overview of the Amber biomolecular simulation package

A re-parameterization of the standard TIP4P water model for use with Ewald techniques is introduced, providing an overall global improvement in water properties relative to several popular nonpolarizable and polarizable water potentials. Using high precision simulations, and careful application of standard analytical corrections, we show that the new TIP4P-Ew potential has a density maximum at approximately 1 degrees C, and reproduces experimental bulk-densities and the enthalpy of vaporization, DeltaH(vap), from -37.5 to 127 degrees C at 1 atm with an absolute average error of less than 1%. Structural properties are in very good agreement with x-ray scattering intensities at temperatures between 0 and 77 degrees C and dynamical properties such as self-diffusion coefficient are in excellent agreement with experiment. The parameterization approach used can be easily generalized to rehabilitate any water force field using available experimental data over a range of thermodynamic points.

/pdf/development-of-an-improved-four-site-water-model-for-10rw432kke.pdf

Development of an improved four-site water model for biomolecular simulations: TIP4P-Ew

Publisher Summary This chapter presents a review of the TIP4P, TIP4P-Ew, TIP5P, and TIP5P-E water models. The advances in simulation techniques have prompted the re-parameterization of earlier water models, which were originally parameterized using older simulation methods. Many of these newly developed water models focused on reproducing speciﬁc properties or a number of properties in a particular phase and other models have been designed to save on computational costs, while some others take advantage of faster computational resources by treating various interactions more effectively. In choosing a water model for use in a molecular simulation, the desired properties of interest must be planned because it will determine which water model would be optimal for the simulation. All the water models presented in the chapter are empirical water models that use a force ﬁeld equation involving only nonbonded terms because the water molecules themselves are rigid. The chapter presents the calculation of the interaction for any of the water molecules with themselves or external inﬂuences and shows the Ewald summation technique to be superior to that of the truncated cut-off method used in simulations.

Chapter 5 A Review of the TIP4P, TIP4P-Ew, TIP5P, and TIP5P-E Water Models

The gaseous and solution phase structures of CO2(aq) are investigated to aid in the development of CO2(aq) MM parameters for use in the CO2 sequestration modeling studies. Previous experimental and computational studies indicate two energetic minima for the interaction of a single CO2 and single water molecule, termed the T-structure and H-structure. For the determination of the energetic minima, ab initio calculations were performed, and the minima were found to have the respective values of −3.0 and −2.1 kcal/mol. From these ab initio calculations, a set of MM parameters were developed to reproduce the gas phase geometry and energetics. The gas-phase parameters were used as starting points in the aqueous phase parameter development, which used free energy perturbation Monte Carlo (FEP/MC) simulations to calculate the solubility of CO2 in aqueous solution as a function of temperature. Parameters were developed for CO2 to be used in the aqueous solution using the TIP3P, TIP4P, and TIP4P-Ew water models. The CO2(TIP4P-Ew) model was found to reproduce the solubility as a function of temperature to within 1% of the experimental solubility. Further testing of the CO2(TIP4P-Ew) model is done in the second part of this work, in which the solubility is calculated in several salt and brine solutions.

CO 2 (aq) Parameterization Through Free Energy Perturbation/Monte Carlo Simulations for Use in CO 2 Sequestration

Free energy perturbation Monte Carlo (FEP/MC) simulations are performed for both the liquid and solid phases of water to determine the melting temperature of several popular three and four-site water models. Gibbs free energy vs. temperature plots are constructed from the simulations to determine the melting temperature. For the liquid phase, standard FEP/MC simulations are used to calculate the free energy relative to the gas phase at multiple temperatures. The free energy of the solid phase relative to the gas phase is calculated at multiple temperatures using the lattice-coupling method. The intersection of the free energy regression lines determines the estimate of the melting temperature. Additionally, simulations were carried out for simple salt solutions to determine the freezing point depressions (FPD). The simulations reproduce the FPD as a function of salt concentration for solutions of NaCl, KCl, CaCl2, and MgCl2.

Free Energy Perturbation Monte Carlo Simulations of Salt Influences on Aqueous Freezing Point Depression

Figure 1. Oblique View of CO2 Interacting with Anthracene. Nanotube Model. Insight II was used to plot the energy profile of the gases within idealized pores, here treated as buckeytubes and buckyballs. In our first case, a nanotube was constructed, as shown in Figure 2. Dummy atoms set along the centerline of the “pore” was used to define a pathway for the molecules. A strong harmonic “pushed” the guest molecule along the defined pathway and the structure allowed to minimize. To save computational expense the “pore” was rigid and did not relax or strain with the passage of the molecule. Step size along the centerline was 0.2 A. The dummy atoms were placed several rings within the tube to reduce “end effects”. The energy of interaction between the host and guess molecule were followed. Similar techniques have been used in Zeolite simulations (3) and are well discussed there.

Thomas J. Dick

Papers

Development of an improved four-site water model for biomolecular simulations: TIP4P-Ew

Chapter 5 A Review of the TIP4P, TIP4P-Ew, TIP5P, and TIP5P-E Water Models

CO 2 (aq) Parameterization Through Free Energy Perturbation/Monte Carlo Simulations for Use in CO 2 Sequestration

Free Energy Perturbation Monte Carlo Simulations of Salt Influences on Aqueous Freezing Point Depression

Molecular Basis for Carbon Dioxide Sequestration in Coal