Large-Scale Biomolecular Chemical Computations toward the Prediction of &lt;i&gt;Burkholderia cepacia&lt;/i&gt; Lipase Enantioselectivity

Yagi, Yoichiro; Tanaka, Takahisa; Imagawa, Atsushi; Moriya, Yosuke; Mori, Yoshihiro; Kimura, Takeyoshi; Kamezawa, Makoto; Naoshima, Yoshinobu

doi:10.15748/jasse.1.141

Cited by 4 publications

(13 citation statements)

References 29 publications

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“…As an alternative to manual preprocessing, an automated preprocessing approach was also initiated by the development working group of the FMODD reported as Auto-FMO protocol (Figure ). As reported from many previous studies, ,,,,− ,, if only a small number of biopolymers are to be subjected to FMO calculation, manual processing using visual inspection and trial and error can be conducted. However, the manual approach is not practical for anything more than a few hundred complexes of drug target proteins and certainly not for the more than 160 000 experimental structures registered in the PDB, so an automatic pretreatment protocol, which was named as Auto-FMO protocol (Figure ), was developed with pipeline pilot .…”

Section: Methodsmentioning

confidence: 99%

FMODB: The World’s First Database of Quantum Mechanical Calculations for Biomacromolecules Based on the Fragment Molecular Orbital Method

Takaya

Watanabe

Nagase

et al. 2021

J. Chem. Inf. Model.

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We developed the world's first web-based public database for the storage, management, and sharing of fragment molecular orbital (FMO) calculation data sets describing the complex interactions between biomacromolecules, named FMO Database (https://drugdesign.riken.jp/FMODB/). Each entry in the database contains relevant background information on how the data was compiled as well as the total energy of each molecular system and interfragment interaction energy (IFIE) and pair interaction energy decomposition analysis (PIEDA) values. Currently, the database contains more than 13 600 FMO calculation data sets, and a comprehensive search function implemented at the front-end. The procedure for selecting target proteins, preprocessing the experimental structures, construction of the database, and details of the database front-end were described. Then, we demonstrated a use of the FMODB by comparing IFIE value distributions of hydrogen bond, ion-pair, and XH/π interactions obtained by FMO method to those by molecular mechanics approach. From the comparison, the statistical analysis of the data provided standard reference values for the three types of interactions that will be useful for determining whether each interaction in a given system is relatively strong or weak compared to the interactions contained within the data in the FMODB. In the final part, we demonstrate the use of the database to examine the contribution of halogen atoms to the binding affinity between human cathepsin L and its inhibitors. We found that the electrostatic term derived by PIEDA greatly correlated with the binding affinities of the halogen containing cathepsin L inhibitors, indicating the importance of QM calculation for quantitative analysis of halogen interactions. Thus, the FMO calculation data in FMODB will be useful for conducting statistical analyses to drug discovery, for conducting molecular recognition studies in structural biology, and for other studies involving quantum mechanics-based interactions.

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Section: Methodsmentioning

confidence: 99%

FMODB: The World’s First Database of Quantum Mechanical Calculations for Biomacromolecules Based on the Fragment Molecular Orbital Method

Takaya

Watanabe

Nagase

et al. 2021

J. Chem. Inf. Model.

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“…In the last few years, we have performed biomolecular chemical simulations, including MD calculation and FMO calculation, on the complexes of BCL and CALB with various primary and secondary alcohol esters. 5,6 We have shown that our simulation is a useful tool for predicting the enantioselectivity of BCL and CALB for various alcohol esters. 5,6…”

Section: Introductionmentioning

confidence: 93%

“…In recent years, we are focusing on biomolecular chemical simulations on the complexes of lipases and organic compounds to predict the enantioselectivity and reactivity of lipase in organic synthesis, and have selected lipases such as Burkholderia cepacia lipase (BCL) and Candida antarctica lipase typeB (CALB) as target proteins. 5,6…”

Section: Introductionmentioning

confidence: 99%

Biomolecular Chemical Simulations on Enantioselectivity and Reactivity of Lipase Enzymes to Azulene Derivatives

Yagi

Kimura²,

Kamezawa³

2022

Natural Product Communications

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Biomolecular chemical simulations have recently become a useful research method in the fields of organic chemistry and bioscience. In the last few years, we have been focusing on the biomolecular computational simulation on lipase enzyme and ligand complexes to predict the enantioselectivity and reactivity of lipases toward non-natural organic compounds. In this paper, we describe the molecular simulations including molecular dynamics (MD) and fragment molecular orbital (FMO) calculations for the complexes of Candida antarctica lipase type A (CALA) and trifluoromethylazulene alcohol derivatives. From the MD calculations, we found that the fast-reacting enantiomer of esters with high enantioselectivity stays in the vicinity of the active site of CALA, while the slow-reacting enantiomer leaves the active site of CALA. On the other hand, both ( R)- and ( S)-enantiomers of ester with low ensntioselectivity were found to keep near to near the active site of CALA. Further, for the esters that do not react with lipase enzyme, we found that both ( R)- and ( S)-enantiomers move away from the active site of lipase enzyme. From the FMO calculations, we found that each fast-reacting enantiomer of esters with high enantioselectivity strongly interacts with certain particular amino acid residues in CALA containing Asp95, while both ( R)- and ( S)-enantiomers of ester with low enantioselectivity interact with same amino acid residues in CALA including Asp95. These results suggest that it is possible to predict not only the enantioselectivity but also the reactivity of CALA and to identify the amino acid residues important to the enzymatic reaction. Therefore, we consider that our computational simulations would be a useful method for predicting and understanding the reactivity and the enantioselectivity of lipase-catalyzed biotransformations.

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“…As shown in our previous works [7,19], the IFIE analysis is a useful method for gaining detailed information on protein-ligand binding. For the esters with high enantioselectivity, each fast reacting enantiomer showed a strong interaction with Thr40 in CALB.…”

Section: Fragment Molecular Orbital Calculationsmentioning

confidence: 99%

“…Over the last several years, we have been focusing our attention on biomolecular chemical simulations of the complexes of lipases with organic compounds to elucidate the enantioselectivity and reactivity of these enzymes in organic synthesis. We have recently shown that both molecular dynamics (MD) and fragment molecular orbital (FMO) calculations are useful means for the prediction of the enantioselectivity of BCL toward a variety of primary and secondary alcohol esters [7]. In this paper, we performed MD and FMO calculations toward CALB complexes with eight different primary alcohol esters ( Figure 1) and thirteen different secondary alcohol esters ( Figure 2).…”

Section: Introductionmentioning

confidence: 99%

<b>Biomolecular Chemical Simulations toward Elucidation of the Enantioselectivity and Reactivity of Lipases in Organic Synthesis</b><b> </b>

Yagi

Kimura²,

Kamezawa³

et al. 2018

CBIJ

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We are presently continuing to perform biomolecular chemical simulations for Burkholderia cepacia lipase (BCL) and Candida antarctica lipase typeB (CALB) to predict their enantioselectivity and reactivity toward various organic compounds. Here, we describe molecular dynamics (MD) and fragment molecular orbital (FMO) calculations on the complexes of CALB with primary and secondary alcohol esters. For esters with high enantioselectivity, the fast-reacting enantiomer of esters is located near the active site of CALB, whereas the slow-reacting enantiomer of esters moves away from the active site of CALB. On the other hand, for the esters with low enantioselectivity, we found that both (R)-and (S)-enantiomers of esters remain the active site of CALB. The FMO computations indicate that for the esters with high enantioselectivity, each fast-reacting enantiomer shows strong interactions with some particular amino acid residues, including Thr40, whereas for the esters with low enantioselectivity, both (R)-and (S)-enantiomers interact with identical amino acid residues including Thr40. It is predictable that Thr40 in CALB plays an important role in the chiral recognition of enantiomers through lipase-catalyzed biotransformations.

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Large-Scale Biomolecular Chemical Computations toward the Prediction of <i>Burkholderia cepacia</i> Lipase Enantioselectivity

Cited by 4 publications

References 29 publications

FMODB: The World’s First Database of Quantum Mechanical Calculations for Biomacromolecules Based on the Fragment Molecular Orbital Method

FMODB: The World’s First Database of Quantum Mechanical Calculations for Biomacromolecules Based on the Fragment Molecular Orbital Method

Biomolecular Chemical Simulations on Enantioselectivity and Reactivity of Lipase Enzymes to Azulene Derivatives

<b>Biomolecular Chemical Simulations toward Elucidation of the Enantioselectivity and Reactivity of Lipases in Organic Synthesis</b><b> </b>

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