An ensemble molecular dynamics method is used to map consensus conformations of the arginine-glycine-aspartic acid (RGD) sequence which are accessible to a set of potent, structurally diverse inhibitors of fibrinogen-glycoprotein IIbIIIa association. This procedure identifies a dominant low-energy RGD conformation that is consistent with the previously determined solution structure of a highly potent RGD-containing peptide. Enforcing an alternate, higher energy conformation is shown to eliminate activity. These observations strongly suggest that the consensus conformation identified is responsible for inhibiting fibrinogen-glycoprotein IIbIIIa binding, thus providing a structural rationale for the de novo design of potent non-peptidal inhibitors of platelet aggregation.