The difference In temperature between the initial and final states is not important, because in this theory the relevant energies (e.g., E^,,) are taken to be temperature Independent.

No abstract

An evaluation of the CHARMm force field for small molecules is described. Using different force field conditions and computational techniques, a wide variety of compounds are analyzed. rms deviations of Cartesian coordinates for 49 diverse organic molecules taken from the Cambridge Crystallographic Data Base and internal coordinate geometries for 28 other molecules are reported. Results are described with different dielectrics, dihedral constraints, and crystal packing to allow analysis of deviations from experimental data and give precise statements of the reliability of the parameters used in the force field. Torsional barriers (rms = 0.4) and conformational energy differences (rms = 0.4) are examined and comparisons made to other force fields such as MM2, Tripos, and DREIDING. The results confirm that CHARMm is an internally consistent all purpose force field with energy terms for bonds, angles, dihedrals, and out-ofplane motions, as well as nonbonded electrostatic and van der Waals interactions. Reported CHARMm results (rms = 0.006 A for bonds, rms = 1.37" for angles, and rms = 3.2" for dihedrals) are in excellent agreement with high quality electron diffraction data. 0 1992 by John Wiley & Sons, Inc.

His-DTrp-Ala-Trp-DPhe-LysNH2, [His1,Lys6] GHRP, is a new synthetic hexapeptide which specifically elicits a dosage-related release of GH in vitro and in vivo without a concomitant release of LH, FSH, TSH, or PRL and, in limited in vivo studies, insulin or glucagon. Our results indicate that this small peptide has the attributes of a hypophysiotropic hormone. In vitro the minimum and maximum active dosages ranged from 1-10 ng/ml in the pituitary incubate assay. It was active in rats, monkeys, lambs, calves, and under special experimental conditions chicks, indicating its lack of species dependency. It was active when administered iv, sc, or ip to rats. After iv injection, GH levels rose within 2 min, peaked at +10-20 min, and by 2 h usually had returned to normal. It was not possible to directly compare the potencies of [His1,Lys6]GHRP, and the GH-releasing factors GHRF-44 and GHRF-40 after a single sc injection in rats because the time course of the GH response of these peptides was different. The GH response of [His1,Lys6]GHRP was longer in duration than either of these larger peptides. Both SRIF-14 and SRIF-28 inhibited the GH response of the hexapeptide; however, SRIF-28 was about four times more active than SRIF-14 in vitro and 7.5 times more active in vivo. When this small peptide was administered sc once or twice daily to immature rats for 9 or 25 days, the BW gain increased above the control. At the end of the weight gain studies the pituitary remained fully responsive to the peptide. Thus, [His1,Lys6] GHRP may be a valuable peptide for investigating the function of the pituitary somatotrophs and, in addition, it has the potential for increasing BW gain of a variety of normal animals by inducing GH release via a direct pituitary site of action.

Crystals of hydrocarbons, carboxylic acids, amines, and amides are used to obtain a self-consistent set of empirical interatomic potentials for the atoms of which polypeptides and proteins are constituted. Simple mathematical forms are adopted for the empirical potential energy functions, and their parameters are determined by a combination of a priori calculations and minimization of the potential energies of the crystal lattices. The partial charges on all atoms are computed by the CNDO/2 (ON) procedure. The coefficients of the attractive (l/r6) term of the Lennard-Jones 6-12 potential are computed by the Slater-Kirkwood method, and the coefficients of the attractive (l/r10 *) term of an empirical general hydrogen bond potential were derived from previous CNDO/2 calculations of hydrogen bond strengths. The coefficients of the repulsive (l/r12) terms of both the Lennard-Jones potential and of the general hydrogen bond potential were obtained by varying these coefficients until the energy-minimized lattice constants agreed as closely as possible with the observed ones. The heavy atoms of the individual molecules in the unit cell were treated as rigid bodies, with no internal degrees of freedom. Their movement in the potential energy minimization procedure was governed by the crystal symmetry operators. The coordinates of the heavy atoms of the molecules were taken directly from the X-ray data, and a procedure was adopted to obtain the coordinates of the hydrogen atoms. The total potential energy function was then used to compute the binding energy of the lattice; in a few cases, some interatomic force constants were computed for interactions between specific pairs of atoms. The computed lattice constants, binding energies, and interatomic force constants are in good agreement with experimental values. Some discussion of the factors governing the determination and the resulting precision of the parameters of the computed potential function is presented.