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Norman L. Allinger

Bio: Norman L. Allinger is an academic researcher from University of Georgia. The author has contributed to research in topics: Hydrogen bond & Molecular mechanics. The author has an hindex of 19, co-authored 26 publications receiving 8766 citations.

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TL;DR: An improved force field for molecular mechanics calculations of the structures and energies of hydrocarbons is presented in this paper, where the problem of simultaneously obtaining a sufficiently large gauche butane interaction energy while keeping the hydrogens small enough for good structural predictions was solved with the aid of onefold and twofold rotational barriers.
Abstract: An improved force field for molecular mechanics calculations of the structures and energies of hydrocarbons is presented. The problem of simultaneously obtaining a sufficiently large gauche butane interaction energy while keeping the hydrogens small enough for good structural predictions was solved with the aid of onefold and twofold rotational barriers. The structural results are competitive with the best of currently available force fields, while the energy calculations are superior to any previously reported. For a list of 42 selected diverse types of hydrocarbons, the standard deviation between the calculated and experimental heats of formation is 0.42 kcal/mol, compared with an average reported experimental error for the same group of compounds of 0.40 kcal/mol. I t has been now amply demonstrated that force field calculations offer the method of choice for the determination of the structures and energies of molecules under many circums t a n c e ~ . ~ ~ While many previously published force fields are very good, they do contain errors which are sufficiently large as to be worrisome to those wishing to utilize them to the fullest possible extent. While the organic chemist is primarily interested in compounds which contain functional groups, since the fundamental structure of organic molecules in general is hydrocarbon in character, a high degree of accuracy in the hydrocarbon part of the force field is crucial. “First generation” force fields showed that one could indeed calculate accurate structures and energies, although the fit to experiment was in some cases less good than one would desire. There has been some difficulty in ascertaining exactly where the force fields were in error, and in which cases the experimental data were less accurate than the probable errors indicated. This question is still not fully answerable but, clearly, more and better data have become available in the last several years. The best we can do is to utilize the existing data, and point out where we feel that there may be errors. We will discuss herein three of the earlier force fields. These are our earlier force field M M l ( 1973)3 and the most recent force fields by Schleyer (EAS)5b and Bartell (MUB-2).6 For all of their usefulness and accuracy, these force fields contained various flaws which showed up in different ways. In an effort to minimize the discrepancy between calculations and experiment, the van der Waals characteristics of atoms were important quantities to be evaluated. In Figure 1 is shown a graph taken mainly from a recent paper by Bartel16 in which the force exerted by a pair of atoms as a function of distance is plotted for several different force fields including MUB-2, EAS, and M M I . For present purposes we will define a “hard” atom as one for which the plot of the force vs. distance for the repulsive part of the curve shows a steep slope (as the dashed C/C line in the figure), and a “soft” atom as one where this slope is more gentle (as the solid line). We will also define a “bigger” atom as one where the line is slid farther to the right, and a “smaller” atom as one for which it is slid to the left. With this terminology, it is seen from the graph that in M M I we used a hydrogen atom which was both rather hard and large compared to that used by Bartell (and other workers), while we used a carbon atom which was small. The “hardness” of our curves was determined by the Hill equation, which is known to fit well for interactions between rare gases.’ There is no assurance that such curves are ideal for carbon and hydrogen atoms which are covalently bound. However, they seemed like a reasonable choice in the absence of definite information. Bartell, mainly on the basis of theory, chose a much softer hydrogen.8 Most other workers have been inclined to follow Bartell’s lead. Bartell’s more recent choice (bVIUB-2) is based on theoretical calculations by Kochanski9 on the Hz molecule. His new hydrogen is larger but softer than the old one. In our early worki0 we noticed that we could not fit adequately to the axial-equatorial methylcyclohexane energy difference using Bartell’s hydrogen, and varying the other parameters that it seemed one might reasonably vary. We therefore continued to use the hard Hill-type hydrogens. Bartell was less anxious to fit this energy difference, and felt he could do a better overall job with structure using soft hydrogens. In each case, the C /H interaction was taken to be the mean of the H / H and C/C interactions. White has also pointed out in a recent paper that our hydrogens are too hard to explain certain data .” We too regard the cyclodecane case which he discusses as a key case, because of the data now available, and it will be discussed below. We

3,313 citations

Journal ArticleDOI
TL;DR: The van der Waals' potentials used for interactions between carbon and hydrogen in both aliphatic and aromatic systems have been improved from those available in MM2, and the new values are used in MM3 as mentioned in this paper.
Abstract: The van der Waals' potentials used for interactions between carbon and hydrogen in both aliphatic and aromatic systems have been improved from those available in MM2, and the new values are used in MM3. The atoms are slightly larger and somewhat softer than they were with MM2. These values were optimized by fitting to the crystal parameters (six cell constants) and the heats of sublimation for the normal alkanes from C6 to C,,, plus C,2, and also diamond, graphite, benzene, biphenyl, and hexamethylbenzene, in addition to fitting structural and energy data on congested molecules as reported earlier. The parameters developed give good crystal structures and heats of sublimation for these molecules. Biphenyl is calculated to be twisted about 40' in the gas phase, but lattice forces cause it to flatten into a planar conformation in the crystal.

860 citations

Journal ArticleDOI
TL;DR: The molecular mechanics (MMP2) program and procedures for the treatment of conjugated hydrocarbons, and some of the results which they can achieve are described in this article.
Abstract: The molecular mechanics (MMP2) program and procedures for the treatment of conjugated hydrocarbons, and some of the results which they can achieve are described. The program is an updated version of the similar MMP1 program, but contains some differences. It is based on an SCF π system calculation, rather than on the VESCF method used earlier. All parameters are compatible with those in the MM2 program. Hence it is possible to calculate heats of formation, resonance energies, and structures for conjugated hydrocarbons in a way that is consistent with the calculations on non-conjugated molecules. The overall results as far as structure and energy are somewhat better than they were with the MMP1 program.

206 citations


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TL;DR: A general Amber force field for organic molecules is described, designed to be compatible with existing Amber force fields for proteins and nucleic acids, and has parameters for most organic and pharmaceutical molecules that are composed of H, C, N, O, S, P, and halogens.
Abstract: We describe here a general Amber force field (GAFF) for organic molecules. GAFF is designed to be compatible with existing Amber force fields for proteins and nucleic acids, and has parameters for most organic and pharmaceutical molecules that are composed of H, C, N, O, S, P, and halogens. It uses a simple functional form and a limited number of atom types, but incorporates both empirical and heuristic models to estimate force constants and partial atomic charges. The performance of GAFF in test cases is encouraging. In test I, 74 crystallographic structures were compared to GAFF minimized structures, with a root-mean-square displacement of 0.26 A, which is comparable to that of the Tripos 5.2 force field (0.25 A) and better than those of MMFF 94 and CHARMm (0.47 and 0.44 A, respectively). In test II, gas phase minimizations were performed on 22 nucleic acid base pairs, and the minimized structures and intermolecular energies were compared to MP2/6-31G* results. The RMS of displacements and relative energies were 0.25 A and 1.2 kcal/mol, respectively. These data are comparable to results from Parm99/RESP (0.16 A and 1.18 kcal/mol, respectively), which were parameterized to these base pairs. Test III looked at the relative energies of 71 conformational pairs that were used in development of the Parm99 force field. The RMS error in relative energies (compared to experiment) is about 0.5 kcal/mol. GAFF can be applied to wide range of molecules in an automatic fashion, making it suitable for rational drug design and database searching.

13,615 citations

Journal ArticleDOI
TL;DR: The results demonstrate that use of ab initio structural and energetic data by themselves are not sufficient to obtain an adequate backbone representation for peptides and proteins in solution and in crystals.
Abstract: 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...

13,164 citations

Journal ArticleDOI
TL;DR: In this paper, 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.
Abstract: 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...

4,722 citations

Journal ArticleDOI
TL;DR: In this paper, a force field for large-scale reactive chemical systems (1000s of atoms) is proposed. But the force field does not have Coulomb and Morse potentials to describe nonbond interactions between all atoms.
Abstract: 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...

4,455 citations

Journal ArticleDOI
Thomas A. Halgren1
TL;DR: The first published version of the Merck molecular force field (MMFF) is MMFF94 as mentioned in this paper, which is based on the OPLS force field and has been applied to condensed-phase processes.
Abstract: 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.

4,353 citations