Fast Estimation Of PK_a Values Of Glu And Asp Amino Acid Residues In Proteins By Using ABEEMσπ Method

In a solution using water as a solvent,the physical quantity used to describe the degree of proton loss is called dissociation constant,which is expressed as pK_a.Therefore,based on the pK_a values of the ionic residues,one can understand the pH-dependent characteristics of the protein and the catalytic mechanism of some enzymes.This article has explored the relationship between the charge distribution and experimental p K_a values,and obtains a linear equation between them.Based on this linear equation,the pK_a values of amino acid residues of biomacromolecular proteins have been predicted.The details are as follows:This thesis selects some ions and molecules containing carboxyl functional groups,and explores the linear relationship between their experimental pK_a and ABEEMσπcharge.The STO-3G basis set and the HF calculation method were employed to calculate the Mulliken charge distributions of the molecules.Valence-state electronegativityχ*,hardness 2η*and initial charge q*have been calibrated by the linear regression and by using the least square method.Using these parameters mentioned above,ABEEMσπmodel was employed to calculate the charge distributions of these molecules.Therefore,the relationships between charges and experimental pK_a values have been explored.Their linear equations have been obtained.For the carboxylic acid molecules,pK_a=-22.053q_O1-4.3717 and for the carboxylate anion q_AC and pK_a,which is the linear equation pK_a=-6.9562q_AC-3.2887.The two linear equations are applied to estimate the pK_a value when the charges q_O1 and q _AC are known.The predicted pK_a values are close to their experimental values.The two linear equations are used to estimate the pK_a values of Asp and Glu amino acids in 15 proteins.They were in order lysozyme（7LYZ,1HEL and 2LZT）,thioredoxin reductase（1TRW）,thioredoxin oxidase（1TRS）,ovomucoid（1OMU）,trypsin bovine（5PTI）,streptococcal protein G（1PGA）,HIV protease（1HPX）,recombinant human insulin（1MHI）,fire egg meleagris gallopavo ovumucin（2OVO）,oxidative thioredoxin（1ERU）,reduced thioredoxin（1ERT）,bovine pancreatic ribonuclease（3RN3）and tuberculin purified protein derivative（1DE3）.The pK_a values of the amino acid Asp and Glu residues in the 15biomacromolecular proteins can be calculated through the linear equations mentioned above.The estimated pK_a values are close to the experimental ones of pK_a.In summary,the atom-bond electronegativity equalization method（ABEEMσπ）can be used to accurately and quickly calculate the charge distributions of the molecules.When the charges are known,the linear equations mentioned above are employed to estimate the pK_a values of the Asp and Glu amino acid residues in the proteins.This provides us a practical method for quickly estimating the pK_a values of amino acid residues in proteins.