Exploring GPCR-Ligand Interactions with the Fragment Molecular Orbital (FMO) Method

2017 ◽  
pp. 179-195 ◽  
Author(s):  
Ewa I. Chudyk ◽  
Laurie Sarrat ◽  
Matteo Aldeghi ◽  
Dmitri G. Fedorov ◽  
Mike J. Bodkin ◽  
...  
Keyword(s):  
Molecular Orbital ◽  
Fragment Molecular Orbital ◽  
Ligand Interactions

scholarly journals Rapid and accurate assessment of GPCR-ligand interactions Using the fragment molecular orbital-based density-functional tight-binding method

2017 ◽  
Vol 38 (23) ◽  
pp. 1987-1990 ◽  
Author(s):  
Inaki Morao ◽  
Dmitri G. Fedorov ◽  
Roger Robinson ◽  
Michelle Southey ◽  
Andrea Townsend-Nicholson ◽  
...  
Keyword(s):  
Molecular Orbital ◽  
Density Functional ◽  
Tight Binding ◽  
Accurate Assessment ◽  
Fragment Molecular Orbital ◽  
Tight Binding Method ◽  
Ligand Interactions

scholarly journals The Fragment Molecular Orbital Method Reveals New Insight into the Chemical Nature of GPCR–Ligand Interactions

2015 ◽  
Vol 56 (1) ◽  
pp. 159-172 ◽  
Author(s):  
Alexander Heifetz ◽  
Ewa I. Chudyk ◽  
Laura Gleave ◽  
Matteo Aldeghi ◽  
Vadim Cherezov ◽  
...  
Keyword(s):  
Molecular Orbital ◽  
Chemical Nature ◽  
Orbital Method ◽  
Molecular Orbital Method ◽  
Fragment Molecular Orbital ◽  
Ligand Interactions ◽  
Insight Into

scholarly journals Analyzing GPCR-Ligand Interactions with the Fragment Molecular Orbital (FMO) Method

2020 ◽  
pp. 163-175
Author(s):  
Alexander Heifetz ◽  
Tim James ◽  
Michelle Southey ◽  
Inaki Morao ◽  
Dmitri G. Fedorov ◽  
...  
Keyword(s):  
Molecular Orbital ◽  
Fragment Molecular Orbital ◽  
Ligand Interactions

scholarly journals Investigation of protein-protein interactions and hot spot region between PD-1 and PD-L1 by fragment molecular orbital method

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hocheol Lim ◽  
Jungho Chun ◽  
Xuemei Jin ◽  
Jongwan Kim ◽  
JeongHyeok Yoon ◽  
...  
Keyword(s):  
Molecular Orbital ◽  
Small Molecule ◽  
Protein Interactions ◽  
Hot Spot ◽  
Immune Surveillance ◽  
Orbital Method ◽  
Protein Protein Interactions ◽  
Fragment Molecular Orbital ◽  
Ligand Interactions ◽  
Interaction Map

Abstract Inhibitors to interfere protein-protein interactions (PPI) between programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) block evasion of cancers from immune surveillance. Analyzing hot spot residues in PPI is important for small-molecule drug development. In order to find out hot spots on PPI interface in PD-1/PD-L1 complex, we analyzed PPI in PD-1/PD-L1 with a new analysis method, 3-dimensional scattered pair interactions energies (3D-SPIEs), which assorts significant interactions with fragment molecular orbital (FMO) method. By additionally analyzing PPI in PD-1/antibody and PD-L1/antibody complexes, and small-ligand interactions in PD-L1/peptide and PD-L1/small-molecule complexes, we narrowed down the hot spot region with 3D-SPIEs-based interaction map, which integrates PPI and small-ligand interactions. Based on the map, there are two hot spot regions in PPI of PD-1/PD-L1 and the first hot spot region is important for inhibitors. In particular, LY56, LE58, and LN66 in the first hot spot of PD-L1 are important for PD-L1-antibodies and small-inhibitors in common, while LM115 is important for small-inhibitors. Therefore, the 3D-SPIEs-based map would provide valuable information for designing new small-molecule inhibitors to inhibit PPI of PD-1/PD-L1 and the FMO/3D-SPIEs method provides an effectual tool to understand PPI and integrate PPI and small-ligand interactions at a quantum mechanical level.

scholarly journals Characterising GPCR–ligand interactions using a fragment molecular orbital-based approach

2019 ◽  
Vol 55 ◽  
pp. 85-92 ◽  
Author(s):  
Alexander Heifetz ◽  
Tim James ◽  
Michelle Southey ◽  
Inaki Morao ◽  
Matteo Aldeghi ◽  
...  
Keyword(s):  
Molecular Orbital ◽  
Fragment Molecular Orbital ◽  
Ligand Interactions

Simulations of Chemical Reactions with the Frozen Domain Formulation of the Fragment Molecular Orbital Method

2015 ◽  
Vol 11 (7) ◽  
pp. 3053-3064 ◽  
Author(s):  
Hiroya Nakata ◽  
Dmitri G. Fedorov ◽  
Takeshi Nagata ◽  
Kazuo Kitaura ◽  
Shinichiro Nakamura
Keyword(s):  
Molecular Orbital ◽  
Chemical Reactions ◽  
Orbital Method ◽  
Molecular Orbital Method ◽  
Fragment Molecular Orbital
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