Antioxidant activity and ACE-inhibitory of Class II hydrophobin from wild strain Trichoderma reesei

International audienceThere are several possible uses of the Class II hydrophobin HFBII in clinical applications. To fully understand and exploit this potential however, the antioxidant activity and ACE-inhibitory potential of this protein need to be better understood and have not been previously reported. In this study, the Class II hydrophobin HFBII was produced by the cultivation of wild type Trichoderma reesei. The crude hydrophobin extract obtained from the fermentation process was purified using reversed-phase liquid chromatography and the identity of the purified HFBII verified by MALDI-TOF (molecular weight: 7.2 kDa). Subsequently the antioxidant activities of different concentrations of HFBII (0.01–0.40 mg/mL) were determined. The results show that for HFBII concentrations of 0.04 mg/mL and upwards the protein significantly reduced the presence of ABTS+ radicals in the medium, the IC50 value found to be 0.13 mg/mL. Computational modeling highlighted the role of the amino acid residues located in the conserved and exposed hydrophobic patch on the surface of the HFBII molecule and the interactions with the aromatic rings of ABTS. The ACE-inhibitory effect of HFBII was found to occur from 0.5 mg/mL and upwards, making the combination of HFBII with strong ACE-inhibitors attractive for use in the healthcare industry

In-Silico Study on the Interaction of Saffron Ligands and Beta-Lactoglobulin by Molecular Dynamics and Molecular Docking Approach

Safranal, crocetin, and dimethylcrocetin are secondary metabolites found in saffron and have a wide range of biological activities. An investigation of their interaction with a transport protein, such as β-lactoglobulin (β-lg), at the atomic level could be a valuable factor in controlling their transport to biological sites. The interaction of these ligands and β-lg as a transport protein was investigated using molecular docking and molecular dynamics (MD) simulation methods. The molecular docking results showed that safranal and crocetin bind on the surface of β-lg. However, dimethylcrocetin binds in the internal cavity of β-lg. The β-lg affinity for binding saffron ligands decreases in the following order: crocetin > dimethylcrocetin > safranal. The analysis of MD simulation trajectories showed that the β-lg and β-lg–ligand complexes became stable at approximately 3000 ps and that there was little conformational change in the β-lg–safranal and β-lg–dimethylcrocetin complexes over a 10-ns timescale. In addition, the profiles of atomic fluctuations showed the rigidity of the ligand binding site during the simulation time

Computer Simulation of the Interaction between SARS-CoV-2 Spike Protein and the Surface of Coinage Metals

A prominent feature of the SARS-CoV-2 virus is the presence of a large glycoprotein spike protruding from the virus envelope. The spike determines the interaction of the virus with the environment and the host. Here, we used an all-atom molecular dynamics simulation method to investigate the interaction of up- and down-conformations of the S1 subunit of the SARS-CoV-2 spike with the (100) surface of Au, Ag, and Cu. Our results revealed that the spike protein is adsorbed onto the surface of these metals, with Cu being the metal with the highest interaction with the spike. In our simulations, we considered the spike protein in both its up-conformation Sup (one receptor binding domain exposed) and down-conformation Sdown (no exposed receptor binding domain). We found that the affinity of the metals for the up-conformation was higher than their affinity for the down-conformation. The structural changes in the spike in the up-conformation were also larger than the changes in the down-conformation. Comparing the present results for metals with those obtained in our previous MD simulations of Sup with other materials (cellulose, graphite, and human skin models), we see that Au induces the highest structural change in Sup, larger than those obtained in our previous studies.This work was supported by Grant PID2021-124297NB-C33 funded by MCIN/AEI/10.13039/501100011033 and, as appropriate, by “ERDF A way of making Europe”, by the “European Union” or by the “European Union NextGenerationEU/PRTR” and by the “Severo Ochoa” Program for Centers of Excellence in R&D (CEX2019-000917-S) awarded to ICMAB. We thank the Spanish national supercomputing network (BSC-RES) for the award of computer time at the Minotauro supercomputer. M .S. is supported by the European Union Horizon 2020 research and innovation programme under Marie Sklodowska-Curie Action Individual Fellowship grant agreement no. 101026158.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe

An investigation of molecular dynamics simulation and molecular docking: Interaction of citrus flavonoids and bovine β-lactoglobulin in focus

Citrus flavonoids are natural compounds with important health benefits. The study of their interaction with a transport protein, such as bovine β-lactoglobulin (BLG), at the atomic level could be a valuable factor to control their transport to biological sites. In the present study, molecular docking and molecular dynamics simulation methods were used to investigate the interaction of hesperetin, naringenin, nobiletin and tangeretin as citrus flavonoids and BLG as transport protein. The molecular docking results revealed that these flavonoids bind in the internal cavity of BLG and the BLG affinity for binding the flavonoids follows naringenin>hesperetin>tangeretin>nobiletin. The docking results also indicated that the BLGflavonoid complexes are stabilized through hydrophobic interactions, hydrogen bond interactions and π-π stacking interactions. The analysis of molecular dynamics (MD) simulation trajectories showed that the root mean square deviation (RMSD) of various systems reaches equilibrium and fluctuates around the mean value at various times. Time evolution of the radius of gyration, total solvent accessible surface of the protein and the second structure of protein showed as well that BLG and BLG-flavonoid complexes were stable around 2500 ps, and there was not any conformational change as for BLG-flavonoid complexes. Further, the profiles of atomic fluctuations indicated the rigidity of the ligand binding site during the simulation

Computational Investigation on Bioluminescence of NanoLuc-Furimamide Complex: Effect of Protonation

International audienc

Computational Studies on the Interaction of Arctiin and Liquiritin With β-lactoglobulin

The study of the interaction of drugs purified from natural sources and a transport protein, such as β-lactoglobulin (BLG), at the atomic level could be a valuable factor to control their transport to biological sites. In the present study, molecular docking and molecular dynamics simulation methods were used to study the interaction of arctiin and liquiritin as natural drugs and BLG as the transport protein. The molecular docking results indicated that these drugs bind in the internal cavity of BLG and the BLG affinity for binding the liquiritin is greater than arctiin. The docking results also indicated that the hydrogen bond interactions have a dominant role in the BLG-drug complex stability. The analysis of MD simulation trajectories showed that the root mean square deviation (RMSD) of BLG-liquiritin, unliganded BLG, and BLG-arctiin reached equilibrium and fluctuated around the mean value at about 1000, 3500, and 4000 ps, respectively. The time evolution of the radius of gyration and total solvent accessible surface of the protein showed that BLG-arctiin and BLG-liquiritin complexes became stable around 2500 and 5000 ps, respectively. Also, the profiles of atomic fluctuations during the simulation showed the rigidity of the ligand binding sites

Molecular Dynamics Simulations of Adsorption of SARS-CoV-2 Spike Protein on Polystyrene Surface

A prominent feature of coronaviruses is the presence of a large glycoprotein spike (S) protruding from the viral particle. The specific interactions of a material with S determine key aspects such as its possible role for indirect transmission or its suitability as a virucidal material. Here, we consider all-atom molecular dynamics simulations of the interaction between a polymer surface (polystyrene) and S in its up and down conformations. Polystyrene is a commonly used plastic found in electronics, toys, and many other common objects. Also, previous atomic force microscopy (AFM) experiments showed substantial adhesion of S over polystyrene, stronger than in other common materials. Our results show that the main driving forces for the adsorption of the S protein over polystyrene were hydrophobic and π–π interactions with S amino acids and glycans. The interaction was stronger for the case of S in the up conformation, which exposes one highly flexible receptor binding domain (RBD) that adjusts its conformation to interact with the polymer surface. In this case, the interaction has similar contributions from the RBD and glycans. In the case of S in the down conformation, the interaction with the polystyrene surface was weaker and it was dominated by glycans located near the RBD. We do not find significant structural changes in the conformation of S, a result which is in deep contrast to our previous results with another hydrophobic surface (graphite). Our results suggest that SARS-CoV-2 virions may adsorb strongly over plastic surfaces without significantly affecting their infectivity.This work was supported by Grant PID2021-124297NB-C33 funded by MCIN/AEI/10.13039/501100011033 and, as appropriate, by “ERDF A way of making Europe”, by the “European Union” or the “European Union NextGenerationEU/PRTR”, and by the “Severo Ochoa” Program for Centers of Excellence in R&D (CEX2019-000917-S) awarded to ICMAB. The authors thank CESGA Supercomputing Center for technical support and computer time at the supercomputers Finisterrae II and III. M.S. is supported by the European Union Horizon 2020 research and innovation programme under Marie Sklodowska-Curie Action Individual Fellowship Grant Agreement No. 101026158.Peer reviewe

Binding of biguanides to β-lactoglobulin: molecular-docking and molecular dynamics simulation studies

Biguanides are a class of drugs derived from biguanide and they are the most widely used drugs for diabetes mellitus or pre-diabetes treatment. An investigation of their interaction and a transport protein such as β-lactoglobulin (BLG) at atomic level could be a valuable factor in controlling their transport to biological sites. Molecular-docking and molecular dynamics simulation methods were used to study the interaction of metformin, phenformin and buformin as biguanides and BLG as transport protein. The molecular-docking results revealed that these biguanides bind to BLG and that the BLG affinity for binding the biguanides decreases in the following order: phenformin — buformin — metformin. The docking results also show the hydrophobic interactions to have a significant role in the BLG-biguanides complex stability. Analysis of molecular dynamic simulation trajectories shows that the root mean square deviation of various systems attained equilibrium and fluctuated around the mean value at various times. The time evolution of the radius of gyration and the total solvent-accessible surface of the protein showed that BLG and BLG-biguanide complexes became stable at approximately 2500 ps and that there was not any conformational change in the BLG-biguanide complexes. In addition, the profiles of atomic fluctuations show the rigidity of the ligand-binding site during the simulation

Dataset: Polystyrene and SARS-CoV-2 S protein MD simulations

Coordinates (input files and equilibrated structures) corresponding to the MD simulations reported in Sahihi and Faraudo, J. Chem. Inf. Model. 2022, 62, 16, 3814–3824 https://doi.org/10.1021/acs.jcim.2c00562 . Please cite this publication and the dataset in any use of the data. The coordinate files in pdb format include fully glycosylated structures of the S1 subunit of SARS-CoV-2 spike protein (up and down confirmations) and a polystyrene slab.European Commission: MAT4COVID - Interaction of SARS-CoV-2 virus with materials: a multi computational simulation study. (101026158)Peer reviewe

Computer Simulation of the interaction between SARS-CoV-2 Spike Protein and the Surface of Coinage Metals

Coinage metals like silver, gold and copper are historically known as materials with anti-infective properties; but the mechanism behind these properties is not yet clear, and several features seem to be effective in this regard. Here, we used an all-atom molecular dynamics simulation method to investigate the interaction of up and down conformations of the S1 subunit of the SARS-CoV-2 spike protein with the (100) surface of Au, Ag and Cu. Our results revealed that spike protein is adsorbed onto the surface of these metals, being the Cu-metal with the highest interaction with the spike and Au, the metal which induces bigger structural changes in the spike. In our simulations, we considered the spike protein in both its up and down conformations. We found that the affinity of the metals for the up-conformation was higher than their affinity for the down conformation of the spike protein due to the interactions with the receptor binding domain that is exposed in the up conformation but hidden in the down conformation. Comparing the present results for metals with those obtained in our previous MD simulations with other materials (cellulose, graphite, and human skin models), we see that Au induces the highest structural change in the spike, larger than those obtained in our previous studies.This work was supported by Grant PID2021-124297NB-C33 funded by MCIN/AEI/ 10.13039/501100011033 and, as appropriate, by “ERDF A way of making Europe”, by the “European Union” or by the “European Union NextGenerationEU/PRTR” and by the “Severo Ochoa” Program for Centers of Excellence in R&D (CEX2019-000917-S) awarded to ICMAB. We thank the Spanish national supercomputing network (BSC-RES) for the award of computer time at the Minotauro supercomputer. M Sahihi is supported by the European Union Horizon 2020 research and innovation programme under Marie Sklodowska-Curie Action Individual Fellowship Grant Agreement No. 101026158.N