The fragment molecular orbital method: theoretical development, implementation in <scp>GAMESS</scp>, and applications

Fedorov, Dmitri G.

doi:10.1002/wcms.1322

Cited by 128 publications

(134 citation statements)

References 184 publications

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“…All quantum mechanical calculations were carried out by using the ab initio FMO method at the RI‐MP2/6‐31G* level of theory implemented in the GAMESS‐US program package …”

Section: Methodsmentioning

confidence: 99%

An insight of early PrP‐E200K aggregation by combined molecular dynamics/fragment molecular orbital approaches

2018

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Unveiling the events leading to the formation of prion particles is a nowadays challenge in the field of neurochemistry. Pathogenic mutants of prion protein (PrP) are characterized by both an intrinsic tendency to aggregation and scrapie conversion propensity. However, the question about a possible correlation between these two events lasts still unanswered. Here, a multilayered computational workflow was employed to investigate structure, stability, and molecular interaction properties of a dimer of PrPC‐E200K, a well‐known mutant of the PrP that represents a reduced model of early aggregates of this protein. Based on the combination of molecular dynamics and quantum mechanical approaches, this study provided for an in depth insight of PrPC‐E200K dimer in terms of residue‐residue interactions. Assembly hypotheses for the early aggregation of PrPC‐E200K are paved and compared with PrPSc models reported in the literature to find a structural link between early and late (scrapie) aggregates of this protein.

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“…All quantum mechanical calculations were carried out by using the ab initio FMO method at the RI‐MP2/6‐31G* level of theory implemented in the GAMESS‐US program package …”

Section: Methodsmentioning

confidence: 99%

An insight of early PrP‐E200K aggregation by combined molecular dynamics/fragment molecular orbital approaches

2018

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“…Secondary structure modeling was performed using the Mfold web server for nucleic acid folding and hybridization prediction . The structures of the aptamers were built by the Avogadro software package, and structure models optimized using the fragment molecular orbital (FMO) method at the level of two‐body FMO expansion . Docking studies of orientation and binding sites of the aptamer‐C‐Met complexes were performed using the AutoDock 4.0 software package (www://autodock.scripps.edu) .…”

Section: Methodsmentioning

confidence: 99%

“…[38] The structures of the aptamers were built by the Avogadro software package, [39] and structure models optimized using the fragment molecular orbital (FMO) method at the level of two-body FMO expansion. [40,41] Docking studies of orientation and binding sites of the aptamer-C-Met complexes were performed using the AutoDock 4.0 software package (www://autodock.scripps.edu). [42] The selected structures with the lowest docking energy of the aptamer are shown in Figure 5.…”

Section: Molecular Docking Of C-met-aptamer Complexesmentioning

confidence: 99%

Molecular Epitope Determination of Aptamer Complexes of the Multidomain Protein C‐Met by Proteolytic Affinity‐Mass Spectrometry

et al. 2020

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C‐Met protein is a glycosylated receptor tyrosine kinase of the hepatocyte growth factor (HGF), composed of an α and a β chain. Upon ligand binding, C‐Met transmits intracellular signals by a unique multi‐substrate docking site. C‐Met can be aberrantly activated leading to tumorigenesis and other diseases, and has been recognized as a biomarker in cancer diagnosis. C‐Met aptamers have been recently considered a useful tool for detection of cancer biomarkers. Herein we report a molecular interaction study of human C‐Met expressed in kidney cells with two DNA aptamers of 60 and 64 bases (CLN0003 and CLN0004), obtained using the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure. Epitope peptides of aptamer‐C‐Met complexes were identified by proteolytic affinity‐mass spectrometry in combination with SPR biosensor analysis (PROTEX‐SPR‐MS), using high‐pressure proteolysis for efficient digestion. High affinities (KD, 80–510 nM) were determined for aptamer‐C‐Met complexes, with two‐step binding suggested by kinetic analysis. A linear epitope, C‐Met (381–393) was identified for CLN0004, while the CLN0003 aptamer revealed an assembled epitope comprised of two peptide sequences, C‐Met (524–543) and C‐Met (557–568). Structure modeling of C‐Met‐aptamers were consistent with the identified epitopes. Specificities and affinities were ascertained by SPR analysis of the synthetic epitope peptides. The high affinities of aptamers to C‐Met, and the specific epitopes revealed render them of high interest for cellular diagnostic studies.

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“…In the fragment molecular orbital (FMO) method, a molecular system is divided into fragments, also called monomers. Fragment calculations are performed in the electrostatic field obtained from the density of all fragments.…”

Section: Introductionmentioning

confidence: 99%

“…Many fragmentation approaches have been developed. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] In the fragment molecular orbital (FMO) method, [24][25][26][27][28] a molecular system is divided into fragments, also called monomers. Fragment calculations are performed in the electrostatic field obtained from the density of all fragments.…”

Section: Introductionmentioning

confidence: 99%

Multithreaded parallelization of the energy and analytic gradient in the fragment molecular orbital method

Mironov

Alexeev

Fedorov

2019

Int J of Quantum Chemistry

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The fragment molecular orbital method in GAMESS is parallelized in a multithreaded OpenMP implementation combined with the MPI version of the two‐level generalized distributed data interface. The energy and analytic gradient in gas phase and the polarizable continuum model of solvation are parallelized in this hybrid three‐level scheme, achieving a large memory footprint reduction and a high parallel efficiency on Intel Xeon Phi processors. The parallel efficiency is demonstrated on the Stampede2 and Theta supercomputers using up to 2048 nodes (262 144 threads).

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The fragment molecular orbital method: theoretical development, implementation in GAMESS, and applications

Cited by 128 publications

References 184 publications

An insight of early PrP‐E200K aggregation by combined molecular dynamics/fragment molecular orbital approaches

An insight of early PrP‐E200K aggregation by combined molecular dynamics/fragment molecular orbital approaches

Molecular Epitope Determination of Aptamer Complexes of the Multidomain Protein C‐Met by Proteolytic Affinity‐Mass Spectrometry

Multithreaded parallelization of the energy and analytic gradient in the fragment molecular orbital method

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