Theoretical Studies on reactions in biological molecules

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Structural data of protein-DNA complex show redundancy and flexibility in base-amino acid interactions. To understand the origin of the specificity in protein-DNA recognition, we calculated the interaction free-energy, enthalpy, entropy and minimum energy maps for AT-Asn, GC-Asn, AF-Ser and GC-Ser by means of a set of ab initio force field with extensive conformational sampling. We found that the most preferable interactions in these pairs are stabilized by hydrogen bonding, and are mainly enthalpy-driven. However, minima in the free energy maps are not necessarily the same as minimum energy map or enthalpy maps, doe to the entrppic effect The effect of entropy is important in the case of GC-Asn. Experimentally observed structures of base-amino acid within preferable regions in the calculated free energy maps, where there are many different configurations with similar energy. The full geometry optimization procedure using ab initio molecular orbital method was applied to get the optimal interaction geometries for AT-Asn, GC-Asn, AF-Ser and GC-Ser. We found that mere are various base-amino acid combinations with similar interaction energies. These results suggest that the redundancy and conformational flexibility in the base-amino acid interactions play an important role in the protein-DNA recognition.Using QM/MM method, we showed that the stable structures (local minima) of molecules in the gas phase are different from those in aqueous solution : a local minimum in the gas phase is not minimum structure in the aqueous solution. It is very important to take account of the solvent explicitly in the calculations. We analyzed how molecules change their conformations by initio MD method.