Computational Chemical Physics Group

Exploring Nature With Computer Simulations

May 11, 2018
by Danilo Roccatano

Modular Assembly of Proteins on Nanoparticles

I have recently contributed to a proof of concept study published in the prestigious  Nature Communication Journal (doi:10.1038/s41467-018-03931-4) [1]. The study involved collaborations with experimental groups across University of Lincoln (UoL), University of Molise (Italy) and the Royal Holloway University of London coordinated by Dr. Enrico Ferrari (UoL).

The motivation for this is that, generally, the high diversity of protein properties necessitates the development of unique nanoparticle bio-conjugation methods, optimized for each different protein. Enrico had the smart idea to design a universal bio-conjugation approach which makes use of a new recombinant fusion protein combining two distinct domains. For this purpose, the N-terminal part is Glutathione S-Transferase (GST, a protein ubiquitously present in both eukaryotes and prokaryotes  with the ability to catalyze the conjugation of the reduced form of glutathione (GSH) to xenobiotic substrates for the purpose of detoxification) from Schistosoma japonicum was bound covalently bound to gold nanoparticles (GNPs) by gold-sulfur bonds. The C-terminal part of this multi-domain construct is the SpyCatcher from Streptococcus pyogenes, which provides the ability to capture recombinant proteins encoding a SpyTag (see Figure 1).


Figure 1: Crystal structure of the SpyCatcher/SpyTag complex (PDB code: 4MLI). The image was created using the Chimera software.

In this work, it was shown that Spy- Catcher can be immobilized covalently on GNPs through GST without the loss of its full functionality. We then show that GST-SpyCatcher activated particles are able to covalently bind a SpyTag modified protein by simple mixing, through the spontaneous formation of an unusual isopeptide bond.

In this paper, Molecular Dynamics (MD) simulations have been used to study the absorption of the protein on the surface of the gold nanoparticles coated with citrate molecules. In the simulation, the nanoparticle surface is approximated as a flat gold surface. An atomistic simulation of the entire particle would be challenging since the NP used in the experimental study (~40 nm in diameter) is too large (only the NP would consist of 2 millions of atoms, see Figure 2).


Figure 2: A 40 nm particle compared to the size of the GST protein. If not differently indicated, all the pictures on this blog have been generated using the VMD software.

Gold nanoparticles are easily produced by reduction of gold salts in the presence of a citrate solution whose concentration determines the diameter of the nanoparticle. The citrate molecules absorbed on the nanoparticle surface negatively charge it. To reproduce this effect, the gold surface used for the MD simulation was prepared by letting citrate molecules to be absorbed on it. In this way, the citrate molecules in complex with Na counterions coat the gold surface as a molecular quill (see Figure 3)!


Figure 3: planar (10×10 nm) Au layer with citrate molecules absorbed used in the simulations.

The result of the simulations clearly indicates the tendency of the protein to bind the coated layer driven by electrostatic interactions with the negative carboxylates of the citrate with the side chain of the arginine residues on the protein surface. In Figure 4, conformations of the protein bonded to the layer at the end of three 20 ns simulations starting from different velocities are shown. The results support the experimental finding on the possible mechanism of absorption of the protein on the nanoparticles.



  1. Ma, A. Saccardo, D. Roccatano, D. Aboagye-Mensah, M. Alkaseem, M. Jewkes, F. Di Nezza, M. Baron, M. Soloviev, E. Ferrari. Modular assembly of proteins on nanoparticles. Nature Communication.9, 1489 (2018).

April 20, 2017
by Danilo Roccatano

Adsorption mechanism of an antimicrobial peptide on carbonaceous surfaces: A molecular dynamics study

 Danilo Roccatano, Edita Sarukhanyan, and Ronen Zangi
The Journal of Chemical Physics 146, 074703 (2017); doi:
jcp_146_7_cover1    Cover Page

Peptides are versatile molecules with applications spanning from biotechnology to nanomedicine. They exhibit a good capability to unbundle carbon nanotubes (CNT) by improving their solubility in water. Furthermore, they are a powerful drug delivery system since they can easily be uptake by living cells, and their high surface to volume ratio facilitates the adsorption of molecules of different nature. Therefore, understanding the interaction mechanism between peptides and CNT is important for designing novel therapeutically agents. In this paper, the mechanisms of the adsorption of antimicrobial peptide Cecropin A – Magainin 2 (CA-MA) on a graphene nanosheet (GNS) and on an ultra-short single-walled CNT are characterized using molecular dynamics simulations. The results show that the peptide coats both GNS and CNT surface through preferential contacts with aromatic side chains. The peptide packs compactly on the carbon surfaces where the polar and functionalize Lys side chains protrude into the bulk solvent. It is shown that the adsorption is strongly correlated to a loss of the peptide helical structure. In the case of the CNT, the outer surface is significantly more accessible for adsorption. Nevertheless when the outer surface is already covered by other peptides, a spontaneous diffusion, via the amidated C-terminus, into the interior of the CNT was observed within 150 ns of simulation time. We found that this spontaneous insertion into the CNT interior can be controlled by the polarity of the entrance rim. For the positively charged CA-MA peptide studied, hydrogenated and fluorinated rims, respectively, hinder and promote the insertion.


April 19, 2017
by Danilo Roccatano

Citrate Synthase a Pac-Enzyme

Citrate Synthase (CS) is an enzyme localized in the mitochondria of our cells where it plays an important role in the aerobic respiration cycle by transforming oxaloacetate molecules (on the right side of the picture) in citrate (on the top left side) with the assistance of the acetyl-coenzyme A (CoA) molecule. As the pac-man in the famous computer game, this Pac-Enzyme diffuse along the space between the convolute cristae of mitochondria “chomping” at its encounter oxaloacetates that activate the enzyme to bind the CoA (ghosts in the playground). For each captured CoA, a new citrate molecule is then produced (score). This complex mechanism requires large conformation changes of parts of the protein (domains) whose molecular details are not yet clarified. Using molecular dynamics simulations on the ARCHER supercomputer, I am studying in collaboration with Dr. S. Hayward of the University of UEA (Norwich, UK) this enzyme to garner novel insights on structural, dynamics and thermodynamics of its functional mechanisms.
The following image was submitted to ARCHER Image Competition 2016
and it was selected for the September picture in the ARCHER calendar 2017.


August 20, 2016
by Danilo Roccatano

Molecular Properties of Astaxanthin in Water/Ethanol Solutions from Computer Simulations

Khadga Jung KarkiSusruta Samanta, and Danilo Roccatano*

J. Phys. Chem. B, August 2016

DOI: 10.1021/acs.jpcb.6b06055

Astaxanthin (AXT) is a reference model of xanthophyll carotenoids, which is used in medicine and food industry, and has potential applications in nanotechnology. Because of its importance, there is a great interest in understanding its molecular properties and aggregation mechanism in water and mixed solvents. In this paper, we report a novel model of AXT for molecular dynamics simulation.

The model is used to estimate different properties of the molecule in pure solutions and in water/ethanol mixtures. The calculated diffusion coefficients of AXT in pure water and ethanol are (3.22 +/- 0.01) 10-6 cm2s-1 and (2.7+/-0.4) 10-6 cm2s-1, respectively. Our simulations also show that the content of water plays a clear effect on the morphology of the AXT aggregation in water/ethanol mixture. In up to 75% (v/v) water concentration, loosely connected network of dimers and trimers, and two-dimensional array structures are observed. At higher water concentrations, AXT molecules form more compact three-dimensional structures that are preferentially solvated by the ethanol molecules. The ethanol preferential binding and the formation of a well connected hydrogen bonding network on these AXT clusters, suggest that such preferential solvation can play an important role in controlling the aggregate structure.


February 3, 2016
by Danilo Roccatano

Invited Seminar at Norwich

On 3rd February 2016, Danilo Roccatano visited the School of Computing Science of the University of East Anglia in Norwich hosted by Dr Steven Hayward. He gave the invited seminar:

Study of Interaction Mechanisms of Block Copolymers with Biological Interfaces


Polyethylene oxide and polypropylene oxide homopolymers, as well as block copolymers based on them (Poloxamers or Pluronics®) have many applications in biotechnology and in pharmacology. This versatility is due to their biocompatibility and tuneable properties. Still, the molecular mechanisms of their interactions with biological systems remain not fully investigated. A powerful and versatile approach to study these processes is the Molecular Dynamics (MD) simulation method that allows exploring these systems on scale of a different order of magnitude in length and time. In the last years, we have developed for these purpose full atoms and coarse-grained models of these polymers that have been successfully tested against several experimental data in solution, and at the interface with lipid bilayers. Using a recently proposed and developedSelf-Consistent density Field MD method, we also accomplished to perform large-scale simulations study of polymeric micelles formation and their interaction with lipid bilayers. These results have unrevealed possible mechanisms of single polymer and micelle interaction with lipid bilayers. In this talk, I will summarize the main achievements and future directions of these studies.