Role of physico-chemical properties of amino acids in protein's structural organization: a network perspective
31 Mar 2012-pp 74-81
TL;DR: The three-dimensional structure of a protein can be described as a graph where nodes represent residues and interactions between them are edges and the highly cliquish hydrophobic nodes in long- and short-range networks play a significant role in bridging and stabilizing distantly placed residues during protein folding.
Abstract: The three-dimensional structure of a protein can be described as a graph where nodes represent residues and interactions between them are edges. We have constructed protein contact networks at different length-scales for different interaction strength cutoffs. The largest connected component of short-range networks exhibit a highly cooperative transition, while long- and all-range networks (more similar to each other), have less cooperativity. The hydrophobic subnetworks in all- and long-range networks have similar phase transition behaviours while hydrophilic and charged networks don't. Hydrophobic subclusters in long- and all-range networks exhibit higher occurrence of assortativity and hence higher communication ability in transmitting information within a protein. The highly cliquish hydrophobic nodes in long- and short-range networks play a significant role in bridging and stabilizing distantly placed residues during protein folding. We have also observed a significant dominance of charged residues cliques in short-range networks.
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TL;DR: In this article , a multi-epitope peptide-based vaccine for non-small-cell lung cancer (NSCLC) utilizing citrullinated peptides was developed.
Abstract: Non-small-cell lung cancer (NSCLC) is the most common lung cancer which has the highest mortality rate in Indonesia. One of the trends in treating cancer is by utilizing peptide vaccines, an immunotherapeutic approach that aims to stimulate the cell-mediated adaptive immune system to recognize cancer-associated peptides. Currently, no peptide vaccines are available in the market for NSCLC treatment. Therefore, this project aims to develop a multi-epitope peptide-based vaccine for NSCLC utilizing citrullinated peptides. Citrullination is a post-translational modification that occurs in cancer cells during autophagy that functions to induce immune responses towards modified self-epitopes such as tumor cells, through activation of PAD enzymes within the APC and target cells. It was found that introducing a common citrullinated neo-antigen peptide such as vimentin and enolase to the immune system could stimulate a higher specific CD4+ T cell response against NSCLC. Moreover, carcinoembryonic antigen (CEA), an antigen that is highly expressed in cancer cells, is also added to increase the vaccine’s specificity and to mobilize both CD4+ and CD8+ T cells. These antigens bind strongly to the MHC Class II alleles such as HLA-DRB1*07:01 and HLA-DRB*11:01, which are predominant alleles in Indonesian populations. Through in silico approach, the peptides generated from CEA, citrullinated vimentin and enolase, were analyzed for their MHC binding strength, immunogenicity, ability to induce IFNγ response, and population coverage. It is expected that the immunodominant antigens presentation is able to induce a potent immune response in NSCLC patients in Indonesia, resulting in tumor eradication.
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TL;DR: This work proposes a model of an assortatively mixed network and finds that networks percolate more easily if they are assortative and that they are also more robust to vertex removal.
Abstract: A network is said to show assortative mixing if the nodes in the network that have many connections tend to be connected to other nodes with many connections. Here we measure mixing patterns in a variety of networks and find that social networks are mostly assortatively mixed, but that technological and biological networks tend to be disassortative. We propose a model of an assortatively mixed network, which we study both analytically and numerically. Within this model we find that networks percolate more easily if they are assortative and that they are also more robust to vertex removal.
4,752 citations
TL;DR: This work transformed protein structures into residue interaction graphs (RIGs), where amino acid residues are graph nodes and their interactions with each other are the graph edges, and found that active site, ligand-binding and evolutionary conserved residues, typically have high closeness values.
463 citations
TL;DR: The hubs identified are found to play a role in bringing together different secondary structural elements in the tertiary structure of the proteins, and could be crucial for the folding and stability of the unique three-dimensional structure of proteins.
389 citations
TL;DR: Geometrical considerations are used to provide a different perspective on the fact that a few selected amino acids act as nucleation centers for protein folding and show that they have the "small-world" feature of having a limited set of vertices with large connectivity.
Abstract: We use geometrical considerations to provide a different perspective on the fact that a few selected amino acids, the so-called "key residues," act as nucleation centers for protein folding. By constructing graphs corresponding to protein structures we show that they have the "small-world" feature of having a limited set of vertices with large connectivity. These vertices correspond to the key residues that play the role of "hubs" in the network of interactions that stabilize the structure of the transition state.
385 citations
TL;DR: It is proposed that centrally conserved residues, whose removal increases the characteristic path length in protein networks, may relate to the system fragility.
Abstract: Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flow of information between amino acids. By removal of nodes from the protein network, we identify fold centrally conserved residues, which are crucial for sustaining the shortest pathways and thus play key roles in long-range interactions. Analysis of seven protein families (myoglobins, G-protein-coupled receptors, the trypsin class of serine proteases, hemoglobins, oligosaccharide phosphorylases, nuclear receptor ligand-binding domains and retroviral proteases) confirms that experimentally many of these residues are important for allosteric communication. The agreement between the centrally conserved residues, which are key in preserving short path lengths, and residues experimentally suggested to mediate signaling further illustrates that topology plays an important role in network communication. Protein folds have evolved under constraints imposed by function. To maintain function, protein structures need to be robust to mutational events. On the other hand, robustness is accompanied by an extreme sensitivity at some crucial sites. Thus, here we propose that centrally conserved residues, whose removal increases the characteristic path length in protein networks, may relate to the system fragility.
315 citations