Abstract：
:Identifying sequence modifications that distinguish psychrophilic from mesophilic proteins is important for designing enzymes with different thermodynamic stabilities and to understand the underlying mechanisms. The PoPMuSiC algorithm is used to introduce, in silico, all the single-site mutations in four mesophilic and one psychrophilic chloride-dependent alpha-amylases and to evaluate the changes in thermodynamic stability. The analysis of the distribution of the sequence positions that could be stabilized upon mutation shows a clear difference between the three domains of psychrophilic and mesophilic alpha-amylases. Most of the mutations stabilizing the psychrophilic enzyme are found in domains B and C, contrary to the mesophilic proteins where they are preferentially situated in the catalytic domain A. Moreover, the calculations show that the environment of some residues responsible for the activity of the psychrophilic protein has evolved to reinforce favorable interactions with these residues. In the second part, these results are exploited to propose rationally designed mutations that are predicted to confer to the psychrophilic enzyme mesophilic-like thermodynamic properties. Interestingly, most of the mutations found in domain C strengthen the interactions with domain A, in agreement with suggestions made on the basis of structural analyses. Although this study focuses on single-site mutations, the thermodynamic effects of the recommended mutations should be additive if the mutated residues are not close in space.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Gilis Ddoi
10.1021/ci050473vsubject
Has Abstractpub_date
2006-05-01 00:00:00pages
1509-16issue
3eissn
1549-9596issn
1549-960Xjournal_volume
46pub_type
杂志文章abstract：:Solute-solvent interactions are critical for biomolecular stability and recognition. Explicit solvent molecular dynamics (MD) simulations are routinely used to probe such interactions. However, detailed analyses and interpretation of the hydration patterns seen in MD simulations can be both complex and time-consuming....
journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
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更新日期：2012-02-27 00:00:00
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更新日期：2008-11-01 00:00:00
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journal_title：Journal of chemical information and modeling
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更新日期：2013-01-28 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章,评审
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci7002945
更新日期：2008-02-01 00:00:00
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journal_title：Journal of chemical information and modeling
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doi：10.1021/ci900286s
更新日期：2009-11-01 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2020-02-24 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci060134h
更新日期：2006-09-01 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci060060+
更新日期：2006-07-01 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00714
更新日期：2017-04-24 00:00:00
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更新日期：2011-09-26 00:00:00
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更新日期：2013-12-23 00:00:00
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journal_title：Journal of chemical information and modeling
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更新日期：2019-03-25 00:00:00
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更新日期：2021-01-14 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2018-06-25 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2006-01-01 00:00:00
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journal_title：Journal of chemical information and modeling
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更新日期：2008-06-01 00:00:00
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