Kim, Straub, and Keyes introduced the statistical temperature molecular dynamics (STMD) algorithm to overcome broken ergodicity by sampling a non­-Boltzmann flat energy histogram as noted in Kim, Straub, and Keyes, Phys. Rev. Lett. 97: 050601 (2007). Canonical averages are calculated via reweighting to the desired temperature. While STMD is promising, its application has been almost entirely to simple or model systems. In this dissertation the implementation of STMD into the biosimulation package CHARMM is used to simulate the methionine enkephalin pentamer peptide with a methione terminal cap in a droplet of CHARMM TIP3P water molecules. Chain thermodynamics is analyzed from the novel perspective of the statistical temperature as a function of potential energy, $TS(U), automatically generated by STMD. Both the minimum in the slope of $TS(U), and the peak in the heat capacity as a function of temperature, calculated via reweighting, indicate a collapse transition at Tθ ≈ 253K. Distributions of dihedral angles are obtained as a function of temperature. Rotamer regions found in the literature are reproduced, along with unique regions not found previously, including with advanced algorithms, indicating the power of STMD enhanced sampling.

This study was designed to explore the hormonal regulation of CNS opioid peptide levels in female Sprague Dawley rats. Forty-eight animals were divided into 2 equal groups for acute and chronic studies. Each group was further divided into 4 subgroups, each containing 6 animals. Each rat in the control group received an inert pill (in 0.25 ml corn oil daily by gavage); the second group, 15 μg norethindrone (NE, a potent progestin present in the oral contraceptive Micronor®); the third group, 15 μg NE and 1 μg ethinyl estradiol, EE2 (present in the oral contraceptive Modicon®) and the fourth group, 10 times the dose of the third group. Rats were treated either acutely for 5 days or chronically for 7 weeks. Opioid peptides were estimated by radioimmunoassay. Acute administration of 150 μg NE + 10 μg EE2 decreased the levels of methionine-enkephalin (ME), leucine-enkephalin (LE), dynorphin (DYN) and β-endorphin like immunoreactivity (β-EI) by about 50% in the pituitary. The same dose on chronic administration also decreased DYN, but increased the levels of ME and LE in the pituitary by 331 and 69%, respectively. In the hypothalamus, chronic administration of NE + EE2 increased the level of ME (155%) and LE (87%) as well as of DYN (97%). In the striatum, the levels of LE (33%) and DYN (115%) were elevated during chronic administration. It is concluded that the acute administration of NE + EE2, in general, reduces the levels of ME, LE, DYN and β-EI. The extent of this decrease is about the same in the pituitary, hypothalamus and striatum. Chronic administration of these hormones, however, results in a reversal of this decrease (except for β-EI) and actually can increase the levels of ME, LE and DYN in all three tissues.