In this area, the O’Brien group is exploring the construction of a novel 3-D fragment library for fragment-based drug discovery. Fragments are relatively simple, small organic molecules with molecular weight of 110-250 Da, clogP values in the range –1 to 3 and total polar surface area of ≤60 Å. However, current fragment libraries are populated with a high proportion of flat, heteroaromatic structures and this can limit the exploration of fragment-protein interactions. To address this, we are designing 3-D fragments that occupy regions of under-represented 3-D pharmaceutical space. Ultimately, the new 3-D fragments are screened against protein targets of relevance to drug discovery. The synthetic element of this project benefits from support from an industrial consortium of partners, including Astex, AstraZeneca, Lilly, Pfizer and Vernalis.