Computational Design of Virus-Like Protein Assemblies on Carbon Nanotube Surfaces

Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science (Impact Factor: 33.61). 05/2011; 332(6033):1071-6. DOI: 10.1126/science.1198841
Source: PubMed


There is a general need for the engineering of protein-like molecules that organize into geometrically specific superstructures on molecular surfaces, directing further functionalization to create richly textured, multilayered assemblies. Here we describe a computational approach whereby the surface properties and symmetry of a targeted surface define the sequence and superstructure of surface-organizing peptides. Computational design proceeds in a series of steps that encode both surface recognition and favorable intersubunit packing interactions. This procedure is exemplified in the design of peptides that assemble into a tubular structure surrounding single-walled carbon nanotubes (SWNTs). The geometrically defined, virus-like coating created by these peptides converts the smooth surfaces of SWNTs into highly textured assemblies with long-scale order, capable of directing the assembly of gold nanoparticles into helical arrays along the SWNT axis.

Full-text preview

Available from:
  • Source
    • "There have also been reports of graphene quantum dot-loaded drugs, but they are not efficient and have not been shown to be useful for any real applications such as tumor treatment1516. The use of graphene-based nanomaterials deserves attention in order to overcome this physiological barrier because these nanomaterials exhibit excellent adsorption properties in the bloodstream171819. Therefore, graphene-based drug delivery nanosystems that are compatible with physiological environments are very desirable. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study aimed to demonstrate that curcumin (Cur)-containing graphene composites have high anticancer activity. Specifically, graphene-derivatives were used as nanovectors for the delivery of the hydrophobic anticancer drug Cur based on pH dependence. Different Cur-graphene composites were prepared based on polar interactions between Cur and the number of oxygen-containing functional groups of respective starting materials. The degree of drug-loading was found to be increased by increasing the number of oxygen-containing functional groups in graphene-derivatives. We demonstrated a synergistic effect of Cur-graphene composites on cancer cell death (HCT 116) both in vitro and in vivo. As-prepared graphene quantum dot (GQD)-Cur composites contained the highest amount of Cur nano-particles and exhibited the best anticancer activity compared to the other composites including Cur alone at the same dose. This is the first example of synergistic chemotherapy using GQD-Cur composites simultaneous with superficial bioprobes for tumor imaging.
    Full-text · Article · Sep 2014 · Scientific Reports
  • Source
    • "We repeat this process of iteratively searching for pairs of residues at a time and incorporating clusters from the search results until we assemble a native-like fragment of a sheet where almost every residue originates from a unique protein structure (two disconnected threonines were inadvertently drawn from the same structure). This then provides α-carbon coordinates that we feed into the backbone search engine MaDCaT [10], which finds suitable scaffolds to incorporate this fragment. One MaDCaT search result greatly resembles the β sheet built using Suns (Figure 4C). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Protein designers use a wide variety of software tools for de novo design, yet their repertoire still lacks a fast and interactive all-atom search engine. To solve this, we have built the Suns program: a real-time, atomic search engine integrated into the PyMOL molecular visualization system. Users build atomic-level structural search queries within PyMOL and receive a stream of search results aligned to their query within a few seconds. This instant feedback cycle enables a new "designability"-inspired approach to protein design where the designer searches for and interactively incorporates native-like fragments from proven protein structures. We demonstrate the use of Suns to interactively build protein motifs, tertiary interactions, and to identify scaffolds compatible with hot-spot residues. The official web site and installer are located at and the source code is hosted at (PyMOL plugin, BSD license), (command line client, BSD license), and (search engine server, GPLv2 license).
    Preview · Article · Jul 2014 · PLoS Computational Biology
  • Source
    • "We herein studied the nanotube surface-induced changes on the conformational structure and bioactivity of rhBMP-2. Singlewalled carbon nanotubes (SWNTs) with unique geometry and tunable hydrophilicity were selected as the model substrate because it is a widely used model to investigate such protein-nanoscaled surface interaction [11] [12]. The adsorption dynamics, the secondary structure, and thereby the bioactivities of rhBMP-2 on both hydrophobic CH 3 -terminated and the hydrophilic COOH-terminated SWNTs (SWNTs-CH 3 , SWNTs-COOH) were investigated in details. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Efficient immobilization of bone morphogenetic protein-2 (BMP-2) onto matrix is of crucial importance in the development of BMP-2-based bone tissue scaffold/implant. This often ties with precise control of desirable protein conformation and retention of protein activity. Recently, great attentions were paid to the regulation of protein conformation by tailoring the nanoscale surface properties. In this contribution, with hydrophilic COOH- and hydrophobic CH3-terminated single-walled carbon nanotubes (SWNTs-COOH and SWNTs-CH3) as models, we investigated the nanoscale interface-induced changes of adsorption dynamics, conformation, and bioactivity of recombinant human BMP-2 (rhBMP-2). Our data showed that SWNTs-COOH and SWNTs-CH3 bound rapidly to and induced unfolding of rhBMP-2 molecules, which promoted their interactions with corresponding receptors on cell surface and thus enhanced their bioactivities. In contrast, rhBMP-2 showed stronger affinity to the COOH-terminated surface than that terminated with CH3 groups, while better enhanced bioactivity on the SWNTs-CH3 surfaces. After released from SWNTs, the unfolded rhBMP-2 refolded and their activities from SWNTs-COOH and SWNTs-CH3 were reduced to 90% and 70% of the native rhBMP-2, respectively. Based on these results obtained, a model of the binding characteristics of rhBMP-2 onto SWNTs with different chemistry is presented. This study demonstrates the possibility of simple tailor-made nanoscale chemical surfaces to modulate the binding, conformation and bioactivity of BMP-2, allowing fabrication of BMP-2-based bone tissue scaffolds with high osteoinductivity and low BMP-2 dosage.
    Preview · Article · Sep 2013 · Biochemical and Biophysical Research Communications
Show more