Proposal of potent inhibitors for vitamin-D receptor based on ab initio fragment molecular orbital calculations

Takeda, Ryosuke; Kobayashi, Ittetsu; Suzuki, Rie; Kawai, Kentaro; Kittaka, Atsushi; Takimoto‐Kamimura, Midori; Kurita, Noriyuki

doi:10.1016/j.jmgm.2018.01.014

Cited by 15 publications

(8 citation statements)

References 29 publications

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“…Currently, FMO allows also to estimate the solvation contribution by interfacing with the polarizable continuum model (PCM) method [4]. The FMO methodology was successfully applied to various large biological systems, primarily in a retrospective analysis of binding sites [5][6][7][8][9][10][11][12][13][14][15][16], but also as a tool supporting drug design [17][18][19][20]. Among these, several studies [7,11,16,18] have focused on one of the most important groups of biological targets, a G protein-coupled receptors (GPCRs) family.…”

Section: Introductionmentioning

confidence: 99%

Recognition of repulsive and attractive regions of selected serotonin receptor binding site using FMO-EDA approach

et al. 2019

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The complexes of selected long-chain arylpiperazines with homology models of 5-HT 1A , 5-HT 2A , and 5-HT 7 receptors were investigated using quantum mechanical methods. The molecular geometries of the ligand-receptor complexes were firstly optimized with the Our own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) method. Next, the fragment molecular orbitals method with an energy decomposition analysis scheme (FMO-EDA) was employed to estimate the interaction energies in binding sites. The results clearly showed that orthosteric binding sites of studied serotonin receptors have both attractive and repulsive regions. In the case of 5-HT 1A and 5-HT 2A two repulsive areas, located in the lower part of the binding pocket, and one large area of attraction engaging many residues at the top of all helices were identified. Additionally, for the 5-HT 7 receptor, the third area of destabilization located at the extracellular end of the helix 6 was found.

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Section: Introductionmentioning

confidence: 99%

Recognition of repulsive and attractive regions of selected serotonin receptor binding site using FMO-EDA approach

et al. 2019

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“…72 Moreover, the FMO method has been shown to be an efficient tool in studies of biological systems. Among many notable examples the most recent ones are the study of potent inhibitors for vitamin-D receptor, 73 the search of novel natural products for prion disease, 63,74 and the study of interaction between sarco/endoplasmic reticulum Ca 2+ -ATPase and its inhibitor thapsigargin toward antimalarial development, 75 as well as mapping interaction energies in chorismate mutase. 76 The FMO method splits a molecular system into individual fragments and describes each fragment in a polarizable Coulomb bath of other fragments.…”

Section: Theoretical Detailsmentioning

confidence: 99%

FMOxFMO: Elucidating Excitonic Interactions in the Fenna–Matthews–Olson Complex with the Fragment Molecular Orbital Method

Kaliakin

Nakata

Kim

et al. 2019

J. Chem. Theory Comput.

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In order to study Förster resonance energy transfer (FRET), the fragment molecular orbital (FMO) method is extended to compute electronic couplings between local excitations via the excited state transition density model, enabling efficient calculations of nonlocal excitations in a large molecular system and overcoming the previous limitation of being able to compute only local excitations. The results of these simple but accurate models are validated against full quantum calculations without fragmentation. The developed method is applied to a very important photosynthetic pigment–protein complex, the Fenna–Matthews–Olson complex (FMOc), that is responsible for the energy transfer from a chlorosome to the reaction center in the green sulfur bacteria. Absorption and circular dichroism spectra of FMOc are simulated, and the role of the molecular environment on the excitations is revealed.

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“…The role of computational approaches is particularly large. Applications for drug discovery using computers include, for example, in silico screening, pharmacophore modeling, and quantum chemistry …”

Section: Introductionmentioning

confidence: 99%

Effect of Structural Descriptors on the Design of Cyclin Dependent Kinase Inhibitors Using Similarity‐based Molecular Evolution

Kawai

Karuo

Tarui

et al. 2020

Molecular Informatics

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In this study, we evaluated the effect of structural descriptors on the in silico design of bioactive compounds. The authors have proposed a molecular design technique for designing new bioactive compounds. In this approach, known fragments are combined to generate new structures, which are evolved to increase the similarity to a known active compound. We generated the structure of CDK2 inhibitors using four descriptors (three binary fingerprints and a numerical vector) to evaluate the effect of descriptors on the molecular design. Subsequently, the physicochemical properties of the generated compounds were com-pared and evaluated from a similarity viewpoint. As a result, it was clarified that better structures can be generated by using descriptors consisting of numerical vectors rather than binary fingerprints. Moreover, the compound generated using the numerical vector or a long-bit fingerprint resulted in favorable docking scores. Although binary fingerprints such as MACCS are widely used in this field, this result shows that it is important to use numeric vectors, or at least to use long-bit fingerprints, to design drug-like CDK2 inhibitors by the similarity-based structure generation.

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Proposal of potent inhibitors for vitamin-D receptor based on ab initio fragment molecular orbital calculations

Cited by 15 publications

References 29 publications

Recognition of repulsive and attractive regions of selected serotonin receptor binding site using FMO-EDA approach

Recognition of repulsive and attractive regions of selected serotonin receptor binding site using FMO-EDA approach

FMOxFMO: Elucidating Excitonic Interactions in the Fenna–Matthews–Olson Complex with the Fragment Molecular Orbital Method

Effect of Structural Descriptors on the Design of Cyclin Dependent Kinase Inhibitors Using Similarity‐based Molecular Evolution

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