Molecular semiconductors have been studied extensively in the literature for use in organic electronic applications. Thousands of diverse structures have been synthesized using organic techniques and often the quest for higher performing materials requires an Edisonian approach. Organic semiconductor structures are generally chosen for their favorable optical and electronic properties but increasingly, molecular shape and planarity are implicated as crucial parameters for dictating functionality in semiconductor devices. The structural units within the semiconductor, responsible for providing the optical and electronic properties, can also be used to control the overall shape and planarity through intramolecular interactions. To investigate these intramolecular interactions prevalent in successful organic semiconductor structures, eight molecules were synthesized to obtain systematic structural changes while maintaining good optoelectronic properties. Using single crystal x-ray crystallography, the conformation of each oligomer was determined. Density functional theory calculations were concomitantly performed for each molecule and the optimized geometry determined. Analysis of interactions within these optimized structures was then completed using rotational barrier calculations and the Natural Bond Orbital analysis. Three major types of intramolecular interactions were revealed: steric, electrostatic and donor-acceptor orbital interactions. Several heteroatomic interactions, including nitrogen—sulfur, nitrogen—hydrogen, and fluorine—sulfur, were found to have large enough energy to cause conformational rigidity, or “locks,” within the molecular structure. These conformational “locks” influence molecular shape, as well as help dictate planarity of the conjugated structures. Critically, these computational data are highly consistent with the observed crytstallographically determined conformation. Through this work, it has become clear that computational approaches to modeling organic semiconductors complement the well-established techniques, such as X-ray crystallography, that chemists currently employ. Importantly, the computational approach provides some predictive capability, which may allow molecules to be screened without time consuming synthetic work. Using these approaches can help chemists design the next class of high performance materials for optoelectronic applications.