Thermostability of Lipase A and Dynamic Communication Based on Residue Interaction Network

2019 ◽  
Vol 26 (9) ◽  
pp. 702-716 ◽  
Author(s):  
Qian Xia ◽  
Yanrui Ding
Keyword(s):  
Time Series ◽  
Active Site ◽  
Interaction Network ◽  
Signal Propagation ◽  
Secondary Structures ◽  
Tight Contact ◽  
Residue Interaction ◽  
Spatio Temporal ◽  
The Relationship ◽  
310 Helix

Objective: Dynamic communication caused by mutation affects protein stability. The main objective of this study is to explore how mutations affect communication and to provide further insight into the relationship between heat resistance and signal propagation of Bacillus subtilis lipase (Lip A). Methods: The relationship between dynamic communication and Lip A thermostability is studied by long-time MD simulation and residue interaction network. The Dijkstra algorithm is used to get the shortest path of each residue pair. Subsequently, time-series frequent paths and spatio-temporal frequent paths are mined through an Apriori-like algorithm. Results: Time-series frequent paths show that the communication between residue pairs, both in wild-type lipase (WTL) and mutant 6B, becomes chaotic with an increase in temperature; however, more residues in 6B can maintain stable communication at high temperature, which may be associated with the structural rigidity. Furthermore, spatio-temporal frequent paths reflect the interactions among secondary structures. For WTL at 300K, β7, αC, αB, the longest loop, αA and αF contact frequently. The 310-helix between β3 and αA is penetrated by spatio-temporal frequent paths. At 400K, only αC can be frequently transmitted. For 6B, when at 300K, αA and αF are in more tight contact by spatio-temporal frequent paths though I157M and N166Y. Moreover, the rigidity of the active site His156 and the C-terminal of Lip A are increased, as reflected by the spatio-temporal frequent paths. At 400K, αA and αF, 310-helix between β3 and αA, the longest loop, and the loop where the active site Asp133 is located can still maintain stable communication. Conclusion: From the perspective of residue dynamic communication, it is obviously found that mutations cause changes in interactions between secondary structures and enhance the rigidity of the structure, contributing to the thermal stability and functional activity of 6B.

scholarly journals Dissecting the evolvability landscape of the CalB active site toward aromatic substrates

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yossef López de los Santos ◽  
Ying Lian Chew-Fajardo ◽  
Guillaume Brault ◽  
Nicolas Doucet
Keyword(s):  
Active Site ◽  
Rational Design ◽  
Interaction Network ◽  
Saturation Mutagenesis ◽  
Rational Approach ◽  
Library Size ◽  
Aromatic Substrates ◽  
Enzyme Substrate ◽  
Residue Interaction ◽  
Enzyme Recognition

Abstract A key event in the directed evolution of enzymes is the systematic use of mutagenesis and selection, a process that can give rise to mutant libraries containing millions of protein variants. To this day, the functional analysis and identification of active variants among such high numbers of mutational possibilities is not a trivial task. Here, we describe a combinatorial semi-rational approach to partly overcome this challenge and help design smaller and smarter mutant libraries. By adapting a liquid medium transesterification assay in organic solvent conditions with a combination of virtual docking, iterative saturation mutagenesis, and residue interaction network (RIN) analysis, we engineered lipase B from P. antarctica (CalB) to improve enzyme recognition and activity against the bulky aromatic substrates and flavoring agents methyl cinnamate and methyl salicylate. Substrate-imprinted docking was used to target active-site positions involved in enzyme-substrate and enzyme-product complexes, in addition to identifying ‘hot spots’ most likely to yield active variants. This iterative semi-rational design strategy allowed selection of CalB variants exhibiting increased activity in just two rounds of site-saturation mutagenesis. Beneficial replacements were observed by screening only 0.308% of the theoretical library size, illustrating how semi-rational approaches with targeted diversity can quickly facilitate the discovery of improved activity variants relevant to a number of biotechnological applications.

scholarly journals Towards a cheminformatic design for quantum mechanical enzyme models: the case of catechol-O-methyltransferase

2020 ◽  
Author(s):  
Thomas Summers ◽  
Qianyi Cheng ◽  
Manuel Palma ◽  
Diem-Trang Pham ◽  
Dudley Kelso III ◽  
...  
Keyword(s):  
Active Site ◽  
Ad Hoc ◽  
Interaction Network ◽  
Quantum Mechanical ◽  
Model Design ◽  
Residue Contact ◽  
Enzyme Models ◽  
Residue Interaction ◽  
Adenosyl Methionine ◽  
Automate Construction

The efficiency, accuracy, and replicability of enzyme simulations is often hampered by ad hoc model design. To address this problem, we have developed the Residue Interaction Network ResidUe Selector (RINRUS) toolkit. RINRUS utilizes residue contact networks to automate construction of rational quantum mechanical cluster models. This work examines this problem by computing the reaction kinetics and thermodynamics for 508 models of the active site of catechol-o-methyltransferase, an enzyme which catalyzes the methyl transfer from S-adenosyl methionine cofactor to catechol substrates. Our results demonstrate using RINRUS to rationally design small and accurate active site models.<br>

scholarly journals Rational, Reproducible, and Rigorous Computational Enzymology: The Case of Catechol-O-Methyltransferase

2020 ◽  
Author(s):  
Thomas Summers ◽  
Qianyi Cheng ◽  
Manuel Palma ◽  
Diem-Trang Pham ◽  
Dudley Kelso III ◽  
...  
Keyword(s):  
Active Site ◽  
Ad Hoc ◽  
Interaction Network ◽  
Quantum Mechanical ◽  
Model Design ◽  
Residue Contact ◽  
Residue Interaction ◽  
Adenosyl Methionine ◽  
Computational Enzymology ◽  
Automate Construction

The efficiency, accuracy, and replicability of enzyme simulations is often hampered by ad hoc model design. To address this problem, we have developed the Residue Interaction Network ResidUe Selector (RINRUS) toolkit. RINRUS utilizes residue contact networks to automate construction of rational quantum mechanical cluster models. This work examines this problem by computing the reaction kinetics and thermodynamics for 508 models of the active site of catechol-o-methyltransferase, an enzyme which catalyzes the methyl transfer from S-adenosyl methionine cofactor to catechol substrates. Our results demonstrate using RINRUS to rationally design small and accurate active site models.<br>

scholarly journals Towards a cheminformatic design for quantum mechanical enzyme models: the case of catechol-O-methyltransferase

2020 ◽  
Author(s):  
Thomas Summers ◽  
Qianyi Cheng ◽  
Manuel Palma ◽  
Diem-Trang Pham ◽  
Dudley Kelso III ◽  
...  
Keyword(s):  
Active Site ◽  
Ad Hoc ◽  
Interaction Network ◽  
Quantum Mechanical ◽  
Model Design ◽  
Residue Contact ◽  
Enzyme Models ◽  
Residue Interaction ◽  
Adenosyl Methionine ◽  
Automate Construction

The efficiency, accuracy, and replicability of enzyme simulations is often hampered by ad hoc model design. To address this problem, we have developed the Residue Interaction Network ResidUe Selector (RINRUS) toolkit. RINRUS utilizes residue contact networks to automate construction of rational quantum mechanical cluster models. This work examines this problem by computing the reaction kinetics and thermodynamics for 508 models of the active site of catechol-o-methyltransferase, an enzyme which catalyzes the methyl transfer from S-adenosyl methionine cofactor to catechol substrates. Our results demonstrate using RINRUS to rationally design small and accurate active site models.<br>

Evolving Fuzzy Time Series for Spatio-temporal Forecasting in Renewable Energy Systems

2021 ◽  
Author(s):  
Carlos A. Severiano ◽  
Petrônio de Cândido de Lima e Silva ◽  
Miri Weiss Cohen ◽  
Frederico Gadelha Guimarães
Keyword(s):  
Time Series ◽  
Renewable Energy ◽  
Energy Systems ◽  
Fuzzy Time Series ◽  
Renewable Energy Systems ◽  
Spatio Temporal

scholarly journals Does a Manager Respond to a Going-Concern Audit Opinion with an Asymmetry in Gain and Loss?

2021 ◽  
Vol 13 (8) ◽  
pp. 4425
Author(s):  
Taewoo Kim
Keyword(s):  
Time Series ◽  
Accounting Conservatism ◽  
Timely Manner ◽  
Audit Opinion ◽  
Going Concern ◽  
Asymmetric Timeliness ◽  
Gain And Loss ◽  
Audit Opinions ◽  
The Relationship

In this paper, I investigate the relationship between previous going-concern audit opinions and subsequent asymmetric timeliness in accounting. Using the time-series and price-based models and conservatism proxy, I find that firms with going-concern audit opinions subsequently report losses in a more timely manner than firms that did not receive going-concern audit opinions. Furthermore, I also find that firms exiting going-concern audit opinions are more likely to report losses rather than gains in a timely manner, compared to firms non-exiting from going-concern opinions. This study extends the prior research by exploring the association between going-concern opinions and accounting conservatism from the perspective of client firms—that is, how firms behave strategically and conservatively to bypass going-concern opinions, once the firms had received previous going-concern opinions.

scholarly journals Novel hydrogen chemisorption properties of amorphous ceramic compounds consisting of p-block elements: exploring Lewis acid-base Al–N pair site formed in-situ within polymer-derived silicon-aluminum-nitrogen-based system

2021 ◽  
Author(s):  
Shotaro Tada ◽  
Norifumi Asakuma ◽  
Shiori Ando ◽  
Toru Asaka ◽  
Yusuke Daiko ◽  
...  
Keyword(s):  
Lewis Acid ◽  
Active Site ◽  
Hydrogen Chemisorption ◽  
Acid Base ◽  
Polymer Derived Ceramics ◽  
System P ◽  
Ceramic Compounds ◽  
The Relationship

This paper reports on the relationship between the H2 chemisorption properties and reversible structural reorientation of the possible active site around Al formed in-situ within polymer-derived ceramics (PDCs) based on...

scholarly journals Adjoint-based direct data assimilation of GNSS time series for optimizing frictional parameters and predicting postseismic deformation following the 2003 Tokachi-oki earthquake

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Masayuki Kano ◽  
Shin’ichi Miyazaki ◽  
Yoichi Ishikawa ◽  
Kazuro Hirahara
Keyword(s):  
Time Series ◽  
Data Assimilation ◽  
Evaluation Method ◽  
Temporal Evolution ◽  
Recovery Process ◽  
Postseismic Deformation ◽  
Coseismic Slip ◽  
Megathrust Earthquakes ◽  
Spatio Temporal ◽  
Gnss Time Series

Abstract Postseismic Global Navigation Satellite System (GNSS) time series followed by megathrust earthquakes can be interpreted as a result of afterslip on the plate interface, especially in its early phase. Afterslip is a stress release process accumulated by adjacent coseismic slip and can be considered a recovery process for future events during earthquake cycles. Spatio-temporal evolution of afterslip often triggers subsequent earthquakes through stress perturbation. Therefore, it is important to quantitatively capture the spatio-temporal evolution of afterslip and related postseismic crustal deformation and to predict their future evolution with a physics-based simulation. We developed an adjoint data assimilation method, which directly assimilates GNSS time series into a physics-based model to optimize the frictional parameters that control the slip behavior on the fault. The developed method was validated with synthetic data. Through the optimization of frictional parameters, the spatial distributions of afterslip could roughly (but not in detail) be reproduced if the observation noise was included. The optimization of frictional parameters reproduced not only the postseismic displacements used for the assimilation, but also improved the prediction skill of the following time series. Then, we applied the developed method to the observed GNSS time series for the first 15 days following the 2003 Tokachi-oki earthquake. The frictional parameters in the afterslip regions were optimized to A–B ~ O(10 kPa), A ~ O(100 kPa), and L ~ O(10 mm). A large afterslip is inferred on the shallower side of the coseismic slip area. The optimized frictional parameters quantitatively predicted the postseismic GNSS time series for the following 15 days. These characteristics can also be detected if the simulation variables can be simultaneously optimized. The developed data assimilation method, which can be directly applied to GNSS time series following megathrust earthquakes, is an effective quantitative evaluation method for assessing risks of subsequent earthquakes and for monitoring the recovery process of megathrust earthquakes.

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