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

Abstract

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.

Molecular Recognition of SARS-CoV-2 Spike Glycoprotein: Quantum Chemical Hot Spot and Epitope Analyses

“…We plan to release all the FMO data in this study on the public database, FMODB, [75][76][77] so that all researchers can access it and utilize it for designing effective antibody-drugs. Also, our group has recently performed over 336 FMO calculations for the COVID-19-related proteins such as S-protein, main protease, RNA-dependent RNA polymerase, 56 based on the representative PDB structures selected in the PDB Japan database in line with this global ght effort against the coronavirus epidemic.…”

“…Also, our group has recently performed over 336 FMO calculations for the COVID-19-related proteins such as S-protein, main protease, RNA-dependent RNA polymerase, 56 based on the representative PDB structures selected in the PDB Japan database in line with this global ght effort against the coronavirus epidemic. These data have already been published on FMODB [75][76][77] and can easily be analyzed IFIEs for inter-and intramolecular interactions on the Web interface. Finally, we expect that these ndings of novel hot spots/epitopes between the SARS-CoV-2 S-protein and ACE2/ B38 Fab antibody will provide useful information for future antibody design, evaluation of the binding property of variant, and small or medium drug design that overcome COVID-19.…”

“…Interaction energy between amino acid residues was evaluated using IFIE analysis with BioStation Viewer. 74 The FMO calculation results of the PDB ID entries 6LZG, 6VW1, 2AJF, and 7BZ5 are registered in the FMO database (FMODB; https://drugdesign.riken.jp/FMODB/) [75][76][77] with its codes (FMODB IDs) as 4NZVN, KR5L3, 596VZ, and Q86GY, respectively.…”

Special Features of COVID-19 in the FMODB: Fragment Molecular Orbital Calculations and Interaction Energy Analysis of SARS-CoV-2-Related Proteins

“…The FMO calculation results of COVID-19-related proteins are available from the top page of the FMODB or the COVID-19 special page. 39 Each FMODB ID page contains information on the used PDB structures and calculation conditions, and the entire dataset, including ABINIT-MP input and output files, can be downloaded. In addition, the binding energies and IFIE/PIEDA energy lists are provided to analyze the interaction data using the web interface.…”

Special feature of COVID-19 in FMODB: Fragment molecular orbital calculations and interaction energy analysis of SARS-CoV-2 related proteins

“…The FMO calculation results of COVID-19-related proteins are available from the top page of FMODB or the COVID-19 special page 8 . Each FMODBID page contains information on the used PDB structures and calculation conditions, and the entire dataset, including ABINIT-MP input and output files, can be downloaded.…”