Many-body Interaction Between The Side Chain Of Amino Acid And Water

Protein is one of the most important substances in life and plays a vital role in many biochemical reactions.Amino acids are the basic unit of protein,and the water environment is essential for biochemical reactions.Therefore,investigations of the interaction between amino acids and water molecules are helpful to explain the mechanism of water molecules participating in protein folding at the molecular level.In this work,44 hydrogen-bonded complexes formed by 6 polar uncharged amino acid side chains and 5 charged amino acid side chains combined with 2-5 water molecules were optimized by MP2/6-311++G(d,p)method.The many-body interaction energies of these complexes were calculated by different methods including the correction of basis set superposition error.The main contents are as follows:1.For the hydrogen-bonded complexes formed by polar uncharged amino acids and water molecules,comparing with the total two-body interaction energies calculated by MP2/aug-cc-p VTZ method,the root mean square error of the corresponding results obtained by the MP2/6-311++G(d,p)method and the MP2/aug-cc-p VDZ method is 3.54 kcal/mol and 2.63 kcal/mol,respectively.For the hydrogen-bonded complexes formed by charged amino acids and water molecules,comparing with the total two-body interaction energies calculated by MP2/aug-cc-p VTZ method,the root mean square error of the corresponding results obtained by the MP2/6-311++G(d,p)method and the MP2/aug-cc-p VDZ method is 3.27 kcal/mol and 2.59 kcal/mol,respectively.The results also show that the total three-body interaction energy calculated by above is not much different.Therefore,the aug-cc-p VTZ basis set was essential in calculating the two-body interaction energy of the hydrogen-bonded complex formed by amino acid and water molecule.2.For hydrogen-bonded complexes formed by polar uncharged amino acids and water molecules,the two-body interaction contributes 70%-90% of the total interaction energy.The contribution of the three-body interaction to the total interaction energy is about 10%-30%.The four-body and higher-order interaction contributes less than 4% to total interaction energy.3.For hydrogen-bonded complexes formed by charged amino acids and water molecules,the contribution of the two-body interaction to the total interaction energy is more than 90%.The contribution of the three-body interaction to the total interaction energy is less than 11%.And the four-body and higher-order interaction is negative contribution,and contributes about 1% to the total interaction energy.4.Based on the MP2/aug-cc-p VTZ method,three density functional theoretical methods were evaluated.The calculation results show that the accuracy of ?B97XD method is best.5.For hydrogen-bonded complexes formed by polar uncharged amino acids and water molecules,as the number of water molecules increases,and the three-body interaction becomes stronger.The portion of three-body interaction energy in total interaction energy increase too.Therefore,in simulating the interaction between amino acids and water,the three-body interaction of water cannot be ignored.