A CGenFF-based force field for simulations of peptoids with both cis and trans peptide bonds.

Peptoids, or poly-n-substituted glycines, are peptide-like polymers composed of a flexible backbone decorated with diverse chemical side chains. Peptoids can form a variety of self-assembling structures based on the type and sequence of the side chains attached to their backbones. All-atom molecular dynamics simulations have been useful in predicting the conformational structures of proteins and will be valuable tools for identifying combinations of peptoid side chains that may form interesting folded structures. However, peptoid models must address a major degree of freedom not common in proteins - the cis/trans isomerization of the peptide bond. This work presents CHARMM general force field (CGenFF) parameters developed to accurately represent peptoid conformational behavior, with an emphasis on a correct representation of both the cis and trans isomers of the peptoid backbone. These parameters are validated against experimental and quantum mechanics data and used to simulate three peptoid side chains in explicitly solvated systems. © 2019 Wiley Periodicals, Inc.

Obesity and angiolymphatic invasion in primary breast cancer.

BACKGROUND: Obesity is associated with poorer breast cancer-specific survival. The purpose of this study was to investigate the relationships between obesity and the presence of angiolymphatic invasion as well as other features of invasive breast cancer, including stage at presentation, estrogen receptor (ER) status, triple-negative phenotype, and tumor grade. METHODS: Detailed clinical and pathologic data were abstracted from the medical records of all 1,312 patients with stage I-III primary breast cancer who had breast surgery at the University of Michigan Comprehensive Cancer Center between January 1, 2000 and December 31, 2006. Bivariate and multivariate analyses were conducted to investigate the relationships between body mass index and tumor biologic features, controlling for menopausal status, diabetes and hypertension, hormone replacement therapy before diagnosis, race, and ethnicity. RESULTS: In multivariate analyses, severe obesity was independently associated with the presence of angiolymphatic invasion [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.08-2.99, joint test of significance, P = 0.03]. Severe obesity was associated with lower likelihood of triple-negative breast cancer (OR 0.39, 95% CI 0.16-0.96). Among premenopausal women with diabetes, ER-negative (OR 5.22, 95% CI 1.12-24.29) and triple-negative (OR 14.8, 95% CI 1.92-113.91) disease was significantly more common. DISCUSSION: In this large sample of invasive breast cancers, obesity was independently associated with the presence of angiolymphatic invasion. Higher rates of angiolymphatic invasion among obese women may account in part for poorer outcomes among obese women with breast cancer.