Phillips conducted various studies on protein structures and their functional implications. He examined the structural features of type 6 streptococcal M proteins, highlighting their predominantly alpha-helical coiled-coil, which demonstrates a unique conformation in bacterial surface projections. His research on the crystal structure of tropomyosin filaments proposed a model in which tropomyosin exhibited distinct conformations related to muscle contraction, suggesting a statistical mechanism for regulating muscle function.
In one of his highly cited studies, Phillips, alongside Fan Yang and Larry G. Moss, described the crystal structure of recombinant wild-type green fluorescent protein, unveiling a unique structure referred to as the "ß-can." This study also delved into the protective environment for the fluorophores within the cylinder and its applications in elucidating the effects of GFP mutants.
Phillips has utilized X-ray crystallography and various advanced spectroscopy techniques to provide details about the dynamic structural changes in proteins. He used X-ray crystallography to determine the structure of unstable intermediate caused by photodissociation of CO from myoglobin and provided insights into the dynamics and structural alterations involved in this protein reaction. In addition, his study focused on capturing the structural evolution of the protein on a picosecond timescale used time-resolved X-ray diffraction and mid-infrared spectroscopy on a myoglobin (Mb) mutant (L29F mutant) revealing conformational changes within the protein.