Application of 1-Aminocyclohexane Carboxylic Acid to Protein Nanostructure Computer Design

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• 作者：Francisco Rodrí ; guez-Ropero ; David Zanuy ; Jordi Casanovas ; Ruth Nussinov ; Carlos Alemá ; n
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2008
• 出版时间：February 2008
• 年：2008
• 卷：48
• 期：2
• 页码：333 - 343
• 全文大小：754K
• 年卷期：v.48,no.2(February 2008)
• ISSN：1549-960X

文摘

Conformationally restricted amino acids are promising candidates to serve as basic pieces in redesignedprotein motifs which constitute the basic modules in synthetic nanoconstructs. Here we study the ability ofconstrained cyclic amino acid 1-aminocyclohexane-1-carboxylic acid (Ac₆c) to stabilize highly regularfchars/beta2.gif" BORDER=0 ALIGN="middle">-helical motifs excised from naturally occurring proteins. Calculations indicate that the conformationalflexibility observed in both the ring and the main chain is significantly higher than that detected for other1-aminocycloalkane-1-carboxylic acids (Ac_nc, where n refers to the size of the ring) with smaller cycles.Incorporation of Ac₆c into the flexible loops of fchars/beta2.gif" BORDER=0 ALIGN="middle">-helical motifs indicates that the stability of such excisedbuilding blocks as well as the nanoassemblies derived from them is significantly enhanced. Thus, the intrinsicAc₆c tendency to adopt folded conformations combined with the low structural strain of the cyclohexanering confers the ability to both self-adapt to the fchars/beta2.gif" BORDER=0 ALIGN="middle">-helix motif and to stabilize the overall structure by absorbingpart of its conformational fluctuations. Comparison with other Ac_nc residues indicates that the ability toadapt to the targeted position improves considerably with the ring size, i.e., when the rigidity introduced bythe strain of the ring decreases.