Strain and interfaces, the susceptibility of fundamental biomolecular building blocks to their intramolecular and intermolecular environment

Peptides and amino acids are fundamental units comprising some of the most important structural and chemical units in biology. Modern analysis of biological matter has underscored the importance of fluctuations in their functions. Accordingly, a thorough understanding of the microscopic degrees of freedom that govern their intermolecular and intramolecular interactions are useful for making predictive assertions, and interpreting observations. The work described in this thesis uses theoretical methods to examine several general aspects of these fluctuations through corresponding susceptibilities to perturbations that have been applied in recent experiments.;Peptide alpha-helicity is one such part of biological structural hierarchy where fluctuations are important. Specifically, side chain fluctuations can produce interesting effects on secondary structure. Our research examines and quantifies the effects of these fluctuations on a coarse-grained a-helix forming peptide. We find that progressively constrained side-chain fluctuations can act on helicity in unobvious ways and can culminate in a breaking of the helicity. Notably, this breaking of helicity by large side chains is distinct from a potential enthalpic breaking of helicity where the volume they exclude is simply too large for hydrogen bonding contacts on the backbone to join.;At a lower level of the structural hierarchy we examine amino acids near flat polar and apolar interfaces. Sum frequency generation spectroscopy provides a suggestive though recondite response that fosters a vague physical depiction of molecule-substrate interactions. Potentials of mean force along the surface normal extracted from molecular dynamics simulations provide fundamental thermodynamic measures affording a quantitative description of amino acids near these interfaces. We further make a qualitative connection between average molecular dipole orientation and electric field environment and how surface-specific response functions might change under changes in temperature.