How the extra methylene group affects the ligation properties of Glu vs. Asp and Gln vs. Asn amino acids: a DFT/PCM study

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• 作者：Todor Dudev ; Lyudmila Doudeva
• 关键词：Asparagine ; Aspartic acid ; DFT calculations ; Glutamic acid ; Glutamine ; PCM computations
• 刊名：Journal of Molecular Modeling
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：23
• 期：2
• 全文大小：
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Computer Applications in Chemistry; Molecular Medicine; Computer Appl. in Life Sciences; Characterization and Evaluation of Materials; Theoretical and Computational Chemistry;
• 出版者：Springer Berlin Heidelberg
• ISSN：0948-5023
• 卷排序：23

文摘

The effect of the extra methylene group on the ligation properties of glutamic (Glu) vs. aspartic (Asp) acid, and glutamine (Gln) vs. asparagine (Asn) amino acids—two pairs of protein building blocks differing by the length of their side chains—has been studied by employing DFT calculations combined with polarizable continuum model (PCM) computations. Complexes of the nominal species with partner ligands of various structures, charge states, and degree of solvent exposure have been examined. The results obtained reveal that the difference in the alkyl chain length of these amino acid residues does not affect the mode of their binding. This, however, influences the thermodynamics of the ligand–ligand and ligand–metal recognition thus bestowing unique ligation characteristics on the competing entities. The calculations reveal that the competition between the longer-chain and shorter-chain analogs is entropy driven and that the differential electronic effects are of minor importance for the process. Thus, the outcome of the rivalry between Asp and Glu, and Asn and Gln is almost unaffected by the nature of the partner ligand, its charge state and, in most cases, the dielectric properties of the binding site. The longer-chain Glu, as opposed to its shorter-chain Asp counterpart, is the preferred partner ligand in various protein binding sites. Contrariwise, the shorter-chain Asn binds more favorably to the respective binding sites than its longer-chain Gln analog. The results obtained shed additional light on the intimate mechanism of the ligand–ligand and ligand–metal recognition in proteins and could be employed as guidelines in protein engineering and design.