New protein parameters are reported for the all-atom empirical energy function in the CHARMM program. The parameter evaluation was based on a self-consistent approach designed to achieve a balance between the internal (bonding) and interaction (nonbonding) terms of the force field and among the solvent−solvent, solvent−solute, and solute−solute interactions. Optimization of the internal parameters used experimental gas-phase geometries, vibrational spectra, and torsional energy surfaces supplemented with ab initio results. The peptide backbone bonding parameters were optimized with respect to data for N-methylacetamide and the alanine dipeptide. The interaction parameters, particularly the atomic charges, were determined by fitting ab initio interaction energies and geometries of complexes between water and model compounds that represented the backbone and the various side chains. In addition, dipole moments, experimental heats and free energies of vaporization, solvation and sublimation, molecular volume...

/pdf/all-atom-empirical-potential-for-molecular-modeling-and-2nds0dxw12.pdf

All-atom empirical potential for molecular modeling and dynamics studies of proteins.

The parametrization and testing of the OPLS all-atom force field for organic molecules and peptides are described. Parameters for both torsional and nonbonded energetics have been derived, while the bond stretching and angle bending parameters have been adopted mostly from the AMBER all-atom force field. The torsional parameters were determined by fitting to rotational energy profiles obtained from ab initio molecular orbital calculations at the RHF/6-31G*//RHF/6-31G* level for more than 50 organic molecules and ions. The quality of the fits was high with average errors for conformational energies of less than 0.2 kcal/mol. The force-field results for molecular structures are also demonstrated to closely match the ab initio predictions. The nonbonded parameters were developed in conjunction with Monte Carlo statistical mechanics simulations by computing thermodynamic and structural properties for 34 pure organic liquids including alkanes, alkenes, alcohols, ethers, acetals, thiols, sulfides, disulfides, a...

https://sakai.rutgers.edu/access/content/user/kparis/biomaps_513_references/02_B_01_JACS118_11225_OPLS.pdf

Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids

A general all-atom force field for atomistic simulation of common organic molecules, inorganic small molecules, and polymers was developed using state-of-the-art ab initio and empirical parametrization techniques. The valence parameters and atomic partial charges were derived by fitting to ab initio data, and the van der Waals (vdW) parameters were derived by conducting MD simulations of molecular liquids and fitting the simulated cohesive energies and equilibrium densities to experimental data. The combined parametrization procedure significantly improves the quality of a general force field. Validation studies based on large number of isolated molecules, molecular liquids and molecular crystals, representing 28 molecular classes, show that the present force field enables accurate and simultaneous prediction of structural, conformational, vibrational, and thermophysical properties for a broad range of molecules in isolation and in condensed phases. Detailed results of the parametrization and validation f...

COMPASS: An ab Initio Force-Field Optimized for Condensed-Phase ApplicationsOverview with Details on Alkane and Benzene Compounds

To make practical the molecular dynamics simulation of large scale reactive chemical systems (1000s of atoms), we developed ReaxFF, a force field for reactive systems. ReaxFF uses a general relationship between bond distance and bond order on one hand and between bond order and bond energy on the other hand that leads to proper dissociation of bonds to separated atoms. Other valence terms present in the force field (angle and torsion) are defined in terms of the same bond orders so that all these terms go to zero smoothly as bonds break. In addition, ReaxFF has Coulomb and Morse (van der Waals) potentials to describe nonbond interactions between all atoms (no exclusions). These nonbond interactions are shielded at short range so that the Coulomb and van der Waals interactions become constant as Rij → 0. We report here the ReaxFF for hydrocarbons. The parameters were derived from quantum chemical calculations on bond dissociation and reactions of small molecules plus heat of formation and geometry data for...

http://www.wag.caltech.edu/publications/sup/pdf/471.pdf

ReaxFF: A Reactive Force Field for Hydrocarbons

This article introduces MMFF94, the initial published version of the Merck molecular force field (MMFF). It describes the objectives set for MMFF, the form it takes, and the range of systems to which it applies. This study also outlines the methodology employed in parameterizing MMFF94 and summarizes its performance in reproducing computational and experimental data. Though similar to MM3 in some respects, MMFF94 differs in ways intended to facilitate application to condensed-phase processes in molecular-dynamics simulations. Indeed, MMFF94 seeks to achieve MM3-like accuracy for small molecules in a combined “organic/protein” force field that is equally applicable to proteins and other systems of biological significance. A second distinguishing feature is that the core portion of MMFF94 has primarily been derived from high-quality computational data—ca. 500 molecular structures optimized at the HF/6-31G* level, 475 structures optimized at the MP2/6-31G* level, 380 MP2/6-31G* structures evaluated at a defined approximation to the MP4SDQ/TZP level, and 1450 structures partly derived from MP2/6-31G* geometries and evaluated at the MP2/TZP level. A third distinguishing feature is that MMFF94 has been parameterized for a wide variety of chemical systems of interest to organic and medicial chemists, including many that feature frequently occurring combinations of functional groups for which little, if any, useful experimental data are available. The methodology used in parameterizing MMFF94 represents a fourth distinguishing feature. Rather than using the common “functional group” approach, nearly all MMFF parameters have been determined in a mutually consistent fashion from the full set of available computational data. MMFF94 reproduces the computational data used in its parameterization very well. In addition, MMFF94 reproduces experimental bond lengths (0.014 A root mean square [rms]), bond angles (1.2° rms), vibrational frequencies (61 cm−1 rms), conformational energies (0.38 kcal/mol/rms), and rotational barriers (0.39 kcal/mol rms) very nearly as well as does MM3 for comparable systems. MMFF94 also describes intermolecular interactions in hydrogen-bonded systems in a way that closely parallels that given by the highly regarded OPLS force field. © 1996 John Wiley & Sons, Inc.

Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94

We report the parameters for a new generic force field, DREIDING, that we find useful for predicting structures and dynamics of organic, biological, and main-group inorganic molecules. The philosophy in DREIDING is to use general force constants and geometry parameters based on simple hybridization considerations rather than individual force constants and geometric parameters that depend on the particular combination of atoms involved in the bond, angle, or torsion terms. Thus all bond distances are derived from atomic radii, and there is only one force constant each for bonds, angles, and inversions and only six different values for torsional barriers. Parameters are defined for all possible combinations of atoms and new atoms can be added to the force field rather simply. This paper reports the parameters for the "nonmetallic" main-group elements (B, C, N, 0, F columns for the C, Si, Ge, and Sn rows) plus H and a few metals (Na, Ca, Zn, Fe). The accuracy of the DREIDING force field is tested by comparing with (i) 76 accurately determined crystal structures of organic compounds involving H, C, N, 0, F, P, S, CI, and Br, (ii) rotational barriers of a number of molecules, and (iii) relative conformational energies and barriers of a number of molecules. We find excellent results for these systems.

DREIDING: A generic force field for molecular simulations

Bacteria that oxidize methane to methanol are central to mitigating emissions of methane, a potent greenhouse gas. The nature of the copper active site in the primary metabolic enzyme of these bacteria, particulate methane monooxygenase (pMMO), has been controversial owing to seemingly contradictory biochemical, spectroscopic, and crystallographic results. We present biochemical and electron paramagnetic resonance spectroscopic characterization most consistent with two monocopper sites within pMMO: one in the soluble PmoB subunit at the previously assigned active site (CuB) and one ~2 nanometers away in the membrane-bound PmoC subunit (CuC). On the basis of these results, we propose that a monocopper site is able to catalyze methane oxidation in pMMO.

Particulate methane monooxygenase contains only mononuclear copper centers

Fe and Ni AB initio effective potentials for use in molecular calculations

From ab initio quality calculations on model systems, we conclude that in unliganded Fe-porphyrin the FE lies in the plane for both the high-spin (q) and intermediate-spin (t) states. Thus, the high-spin d6 Fe is not too big to fit into the porphyrin plane (as often suggested). We find the q state lower for a porphyrin hole radius greater than 1.94 A and the t state lower for smaller sizes. For the five-coordinate complex including an axial nitrogenous ligand [a model for myoglobin (Mb) and hemoglobin (Hb)], we find the ground state to be q with the Fe 0.3 A out of the plane (recent x-ray data on deoxy Mb suggests about 0.4 A). The origin of this out-of-plane displacement is the nonbonded repulsions between the axial ligand and porphyrin nitrogen orbitals. Pushing the Fe of the five-coordinate complex into the plane does not lead to a stable low-spin state (as usually suggested), the q and t states being the low-lying states. Bonding the O2 to form the six-coordinate complex stabilizes the t form of the Mb model, leading to a singlet state of MbO2 with Fe in the plane. (It has often been suggested that the Fe of MbO2 and HbO2 is low-spin Fe2+; however, we find this not to be the case.) The bonding in the MbO2 model confirms the ozone model of the bonding, leading to a structure consistent with the Pauling model (our calculated FeOO bond angle is 119 degrees). The total charge transfer to the O2 is 0.10 electron, in disagreement with the Weiss model. Molecular orbital calculations (Hartree-Fock) incorrectly lead to septet ground state (S = 3) for the MbO2 model. The implications for the cooperative O2 binding in hemoglobin and protein modifications of the energetics of the active site are considered. Use of our calculated force constants for displacement of Fe perpendicular to the heme plane suggests that the movement of the Fe upon a change in the quaternary structure from the T to the R form is only about 0.04 A toward the heme plane.

https://www.pnas.org/content/pnas/74/4/1315.full.pdf

Molecular description of dioxygen bonding in hemoglobin

Several rather different models of the Fe—O2 bond in oxyhemoglobin have previously been proposed, none of which provide a satisfactory explanation of several properties. We propose a new model for the bonding of an O2 to the Fe of myoglobin and hemoglobin and report ab initio generalized valence bond and configuration interaction calculations on FeO2 that corroborate this model. Our model is based closely upon the bonding in ozone which recent theoretical studies have shown to be basically a biradical with a singlet state stabilized by a three-center four-electron pi bond. In this model, the facile formation and dissociation of the Fe—O2 bond is easily rationalized since the O2 always retains its triplet ground state character. The ozone model leads naturally to a large negative electric field gradient (in agreement with Mossbauer studies) and to z-polarized (perpendicular to the heme) charge transfer transitions. It also suggests that the 1.3 eV transition, present in HbO2 and absent in HbCO, is due to a porphyrin-to-Fe transition, analogous to that of ferric hemoglobins (e.g., HbCN).

https://www.pnas.org/content/pnas/72/6/2335.full.pdf

Barry D. Olafson

Papers

DREIDING: A generic force field for molecular simulations

Particulate methane monooxygenase contains only mononuclear copper centers

Fe and Ni AB initio effective potentials for use in molecular calculations

Molecular description of dioxygen bonding in hemoglobin

Ozone model for bonding of an O2 to heme in oxyhemoglobin.