The TATA binding protein (TBP) is a basal transcription factor that binds specifically to the minor groove of TATA boxes. TBP is required for efficient recruitment of the transcription machinery, as it bends DNA, generating binding sites for TFIIB and RNA polymerase II. Only ∼10% of human protein coding genes possess a TATA box, and TBP is required for the transcription of the more common TATA-less genes also. We explored the energy contributions to TBP binding of a collection of 16 repeating DNA sequences, in a productive bent conformation. Binding energy is dominated by the cost of deforming DNA from the straight, B-DNA reference, to the conformation found in the complex. Interestingly, there is a positive correlation between the deformation energy of DNA and the interaction energy of DNA with TBP: poor interaction energies, derived mainly from avoided clashes with guanine amino groups and hydrophobic TBP sidechains, lead to greater deformation energies, due to clashes between exocyclic groups at the major groove of DNA. In order to uncouple deformation and interaction, we substituted guanines with inosines, eliminating putative clashes at the minor groove while keeping the major groove chemistry. Improving the interaction also ameliorated the deformation cost. Large deformation costs are incurred because we kept the complex structure fixed to a productive conformation. As high affinity binding has been shown not to be correlated always to transcription efficiency, we carried out molecular dynamics simulations of three TBP-DNA complexes, with alternating TA, CG and CI sequences. Preliminary results suggest that a large deformation cost is relieved by relaxing both TBP and DNA structures, generating increasingly unproductive complex structures.Funding: Macroproyecto de Tecnologias de la Informacion y la Computacion (UNAM). SEP-FOMES 2000 (Computo Cientifico), and CONACyT (91209 AC1).