On the induced‐fit mechanism of substrate‐enzyme binding structures of nylon‐oligomer hydrolase |
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| Authors: | Takeshi Baba Ryuhei Harada Masayoshi Nakano Yasuteru Shigeta |
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| Affiliation: | 1. Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Toyonaka, Japan;2. RIKEN, Advanced Institute for Computational Science, Chuo‐Ku, Kobe, Hyogo, Japan;3. JST, CREST, Kawaguchi, Saitama, Japan |
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| Abstract: | We present a detailed computational investigation of the induced‐fit motion in a nylon‐oligomer hydrolase (NylB) upon substrate binding. To this aim, we resort on the recently introduced parallel cascade selection molecular dynamics approach, allowing for an accelerated access to the set of conformational changes from an open‐ to a closed‐state structure to form the enzyme‐substrate complex in a specific induce‐fit mechanism. The structural investigation is quantitatively complemented by free energy analyses within the umbrella sampling algorithm accompanied by weighted histogram analysis. We find that the stabilization free energy is about 1.4 kcal/mol, whereas the highest free energy barrier to be overcome is about 2.3 kcal/mol. Conversely, the energetic contribution for the substrate binding is about 20 kcal/mol, as estimated from Generalized Born/Surface Area. This means that the open‐close induced‐fit motion could occur frequently once the substrate binds to the open state of NylB. © 2014 Wiley Periodicals, Inc. |
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| Keywords: | induced‐fit enzyme‐substrate binding nylon‐oligomer hydrolase NylB parallel cascade selection molecular dynamics free energy landscape |
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