Computational Insights into Dynamics of Protein Aggregation and Enzyme鈥揝ubstrate Interactions

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• 作者：Mehmet Ozbil ; Arghya Barman ; Ram Prasad Bora ; Rajeev Prabhakar
• 刊名：The Journal of Physical Chemistry Letters
• 出版年：2012
• 出版时间：December 6, 2012
• 年：2012
• 卷：3
• 期：23
• 页码：3460-3469
• 全文大小：582K
• 年卷期：v.3,no.23(December 6, 2012)
• ISSN：1948-7185

文摘

In this Perspective, the roles of protein dynamics have been discussed in the aggregation of amyloid beta (A尾) peptides and formation of enzyme鈥搒ubstrate complexes of beta-secretase (BACE1) and insulin-degrading enzyme (IDE). The studies regarding the influence of individual amino acid residues and specific regions on the structures and oligomerization of early A尾 aggregates and computations of their translational and rotational diffusion coefficients and order parameters exhibited that even the short-time-scale molecular dynamics simulations can reproduce certain experimental parameters with reasonable accuracy. The simulations elucidating the enzyme鈥搒ubstrate interactions of BACE1 and IDE successfully showed that the chemical nature and length of the substrates influence the dynamics and plasticity of both the enzyme and substrate. An atomic-level understanding of these processes will advance our efforts to develop therapeutic strategies for several deadly diseases through the design of small molecules with antiaggregation properties and substrate-specific 鈥渄esigner鈥?forms of enzymes.