A complete set of intermolecular potential functions has been developed for use in computer simulations of proteins in their native environment. Parameters are reported for 25 peptide residues as well as the common neutral and charged terminal groups. The potential functions have the simple Coulomb plus Lennard-Jones form and are compatible with the widely used models for water, TIP4P, TIP3P, and SPC. The parameters were obtained and tested primarily in conjunction with Monte Carlo statistical mechanics simulations of 36 pure organic liquids and numerous aqueous solutions of organic ions representative of subunits in the side chains and backbones of proteins. Bond stretch, angle bend, and torsional terms have been adopted from the AMBER united-atom force field. As reported here, further testing has involved studies of conformational energy surfaces and optimizations of the crystal structures for four cyclic hexapeptides and a cyclic pentapeptide. The average root-mean-square deviation from the X-ray structures of the crystals is only 0.17 A for the atomic positions and 3% for the unit cell volumes. A more critical test was then provided by performing energy minimizations for the complete crystal of the protein crambin, including 182 water molecules that were initially placed via a Monte Carlo simulation. The resultant root-mean-square deviation for the non-hydrogen atoms is still ca. 0.2 A and the variation in the errors for charged, polar, and nonpolar residues is small. Improvement is apparent over the AMBER united-atom force field which has previously been demonstrated to be superior to many alternatives. Computer simulations are undoubtedly destined to became an increasingly important means for investigating the structures and dynamics of biomolecular systems.' At the heart of such theoretical calculations are the force fields that describe the interatomic interactions and the mechanics of deformations of the molecules.* There is also little doubt that there will be a continual evolution in force fields with added complexity and improved performance paralleling the availability of computer resources. Our own efforts in this area over the last few years have resulted in the OPLS potential functions for proteins whose development and performance are summarized here. These potential functions have a simple form and they have been parametrized directly to reproduce experimental thermodynamic and structural data on fluids. Consequently, they are computationally efficient and their description of proteins in solution or crystalline environments should be superior to many alterantives that have been developed with limited condensed-phase data. The latter point is pursued here primarily through calculations on the crystal structures for four cyclic hexapeptides, a cyclic pentapeptide, and the protein crambin. Improvements are apparent in comparison to the AMBER united-atom force field3 which has previously been shown to be superior to many alternative^.^ (1) Beveridge, D. L., Jorgensen, W. L., Eds. Ann. N.Y. Acad. Sci. 1986, 482. ( 2 ) For reviews, see: (a) Levitt, M. Annu. Reu. Biophys. Eioeng. 1982, 11, 251. (b) McCammon, J. A. Rep. Prog. Phys. 1984, 47, 1. (3) Weiner, S. J.; Kollman, P. A.; Case, D. A,; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta, S.; Weiner, P. J. Am. Chem. SOC. 1984, 106, 765. Parametrization The peptide residues of proteins contain readily identifiable organic subunits such as amides, hydrocarbons, alcohols, thioethers, etc. In view of this and since data are available on the corresponding pure organic liquids, our approach to developing a force field for proteins was to build it up from parameters demonstrated to yield good descriptions of organic liquids. U1timately, the force field would need to treat both intramolecular terms for bond stretches, angle bends, and torsions, as well as the intermolecular and intramolecular nonbonded interactions. The latter are generally accepted to be the most difficult part of the problem and have been our focus.3 A simple, computationally efficient form was chosen to represent the nonbonded interactions through Coulomb and Lennard-Jones terms interacting between sites centered on nuclei (eq 1). Thus, the intermolecular inter-

The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin.

We present an all atom potential energy function for the simulation of proteins and nucleic acids. This work is an extension of the CH united atom function recently presented by S.J. Weiner et al. J. Amer. Chem. Soc., 106, 765 (1984). The parameters of our function are based on calculations on ethane, propane, n−butane, dimethyl ether, methyl ethyl ether, tetrahydrofuran, imidazole, indole, deoxyadenosine, base paired dinucleoside phosphates, adenine, guanine, uracil, cytosine, thymine, insulin, and myoglobin. We have also used these parameters to carry out the first general vibrational analysis of all five nucleic acid bases with a molecular mechanics potential approach.

An all atom force field for simulations of proteins and nucleic acids.

On the function and mechanism of action of peroxidases

Bacteriorhodopsin and the purple membrane of halobacteria

1 – Optical Spectra and Electronic Structure of Porphyrins and Related Rings

Raman spectra have been obtained for n‐butane, 2‐methylbutane, and 2, 3‐dimethylbutane in the vapor and solid (−196°C) phases. The low temperature spectra of the solids undergo a marked simplification due to the disappearance of all but one of the rotational isomers. This enabled band pairs in the vapor spectrum to be identified with the appropriate rotational isomers. From the temperature dependence of selected band pairs the enthalpy difference between the rotational isomers was obtained for each compound in the vapor phase.

Rotational isomerism. XI. Raman spectra of n-butane, 2-methylbutane, and 2, 3-dimethylbutane

Spectroscopic studies of rhodamine 6G dispersed in polymethylcyanoacrylate

Resonance Raman spectra of copper‐porphin in solution have been obtained using the tunable rhodamine 6G dye, Ar+, and HeCd lasers for excitation. Several bands show variation of intensity with excitation wavelength and many combination and overtone bands have been observed with 5145 A excitation. Depolarization ratios for the two anomalously polarized bands [ρl > (3/4)] at 1322 and 1587 cm−1 remain constant (∼45) with all the exciting wavelengths in the α and β absorption regions while some polarized bands show variation of their ρl values. It is shown that the rigorous molecular symmetry of Cu‐porphin in solution is D4h. Symmetry species of the vibrational modes have been assigned.

Resonance Raman spectra of copper‐porphin

Resonance Raman spectra have been obtained for the Ni, Co, and Cu chelates of mesoporphyrin IX dimethyl ester in solution using the tunable Rhodamine 6G dye and Ar+ lasers. Several bands show variation of intensity and depolarization ratio with exciting wavelength. Excitation profiles for some isolated bands peak at the maxima of the corresponding α electronic absorption bands. The variation of depolarization ratio for some anomalously polarized bands (ρl > 3/4) has been interpreted in terms of lowering of the symmetry of metalloporphyrins from D4h. The rigorous symmetry of these chelates is proposed as Cs because of the effect of peripheral substituents. A vibrational assignment is suggested for some of the metal sensitive modes.

A. L. Verma

Papers

Rotational isomerism. XI. Raman spectra of n-butane, 2-methylbutane, and 2, 3-dimethylbutane

Spectroscopic studies of rhodamine 6G dispersed in polymethylcyanoacrylate

Resonance Raman spectra of copper‐porphin

Resonance Raman spectra of the nickel, cobalt, and copper chelates of mesoporphyrin IX dimethyl ester

Hydrogen peroxide vapor sensor using metal-phthalocyanine functionalized carbon nanotubes