2016
DOI: 10.1042/bst20150250
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Using the fragment molecular orbital method to investigate agonist–orexin-2 receptor interactions

Abstract: The understanding of binding interactions between any protein and a small molecule plays a key role in the rationalization of affinity and selectivity and is essential for an efficient structure-based drug discovery (SBDD) process. Clearly, to begin SBDD, a structure is needed, and although there has been fantastic progress in solving G-protein-coupled receptor (GPCR) crystal structures, the process remains quite slow and is not currently feasible for every GPCR or GPCR–ligand complex. This situation significa… Show more

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Cited by 33 publications
(31 citation statements)
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“…The interactions detected by FMO‐DFTB are consistent with the experimental data and with those detected by FMO‐MP2 . The application of FMO‐DFTB will be of great utility for the design and evaluation of new compounds, providing a means of significantly decreasing the effort and cost of chemical synthesis needed for drug discovery programs . The high correlation between receptor‐ligand experimentally evaluated affinity and TIE FMO ‐DFTB indicates that FMO‐DFTB can be used to determine the binding affinities of new targets and, therefore, provides a means of accurately predicting experimental outcomes.…”
Section: Introductionsupporting
confidence: 72%
“…The interactions detected by FMO‐DFTB are consistent with the experimental data and with those detected by FMO‐MP2 . The application of FMO‐DFTB will be of great utility for the design and evaluation of new compounds, providing a means of significantly decreasing the effort and cost of chemical synthesis needed for drug discovery programs . The high correlation between receptor‐ligand experimentally evaluated affinity and TIE FMO ‐DFTB indicates that FMO‐DFTB can be used to determine the binding affinities of new targets and, therefore, provides a means of accurately predicting experimental outcomes.…”
Section: Introductionsupporting
confidence: 72%
“…Recently, an approximate molecular orbital (MO) method called Fragment Molecular Orbital (FMO) was implemented into studies related to GPCR-ligand interactions [60][61][62][63][64][65][66][67][68]. FMO has been described in previous publications and review articles [60][61][62].…”
Section: The Qm Approach In Gpcr Studiesmentioning
confidence: 99%
“…The theoretical characterization of ligand-binding recognition in GPCRs exhibited similar electrostatic and hydrophobic interactions across most GPCR complexes. In 2016, Heifetz and coworkers performed the FMO calculation on the complexes of agonist-orexin-2 receptor (OX 2 R) [64]. They considered all interactions with an absolute pair interaction energy (PIE) greater than or equal to 3.0 kcal/mol.…”
Section: The Qm Approach In Gpcr Studiesmentioning
confidence: 99%
“…The FMO method is already recognized as a useful drug design tool to analyze ligand binding interactions, incorporating electrostatic interactions such as hydrogen bonds and dispersion forces such as CH/π interactions, using the pair interaction energy decomposition analysis (PIEDA) [4,5] and fine fragmentation by the functional group unit, rather than the amino acid residue unit and the whole ligand [6][7][8]. Recently, the IFIE analysis and its energy decomposition analysis have been applied to the prediction of binding affinity for rational drug design [9][10][11][12][13][14][15][16][17][18]. Using FMO calculations of tens of complexes for one target protein, the essential and characteristic interactions of the ligand binding mode can be abstracted from the IFIE and PIEDA data by clustering methods [19][20] and singular value decomposition [21].…”
Section: Introductionmentioning
confidence: 99%