Free-Energy Maps of Base−Amino Acid Interactions for DNA−Protein Recognition

Abstract

DNA−protein recognition plays a central role in gene expression and regulation. Despite increasing structural data on DNA−protein complexes, the molecular mechanism of DNA−protein recognition is not well understood yet, partly because of the considerable extent of redundancy in the base−amino acid interactions as well as of the structural flexibility present within the same interaction pair. To understand the specificity of such interactions, we should examine the interaction energetics by taking account of the structural flexibility. We describe a strategy for elucidating the specificity of DNA−protein interactions by computer simulation, in which free energies of interactions between the amino acid side chains and base pairs are computed by extensive conformational sampling. The simulations enable us to estimate thermodynamic quantities, such as the interaction free energy, enthalpy, and entropy, for each given position of the Cα atom of the amino acid side chain by conformational averaging, and to eval...