A network representation of protein structures: implications to protein stability

¹ Indian Institute of Science

^* To whom correspondence should be addressed. E-mail: sv{at}mbu.iisc.ernet.in.

Submitted on April 11, 2005
Revised on May 22, 2005
Accepted on 9 August 2005

	Abstract

The present study views each protein structure as a network of non-covalent connections between amino acid side chains. Each amino acid in a protein structure is a node and the strength of the non-covalent interactions between two amino acids is evaluated for edge determination. The Protein structure graphs (PSGs) for 232 proteins have been constructed as a function of the cutoff of the amino acid interaction strength at a few carefully chosen values. Analysis of such PSGs constructed on the basis of edge weights has shown that (1) The PSGs exhibit a complex topological network behavior, which is dependent on the interaction cutoff chosen for PSG construction. (2) A transition is observed at a critical interaction cutoff, in all the proteins, as monitored by the size of the largest cluster (giant component) in the graph. Amazingly, this transition occurs within a narrow range of interaction cutoff for all the proteins, irrespective of the size or the fold topology. (3) The amino acid preferences to be highly connected (hub frequency) has been evaluated as a function of the interaction cutoff. We observe that the aromatic residues along with Arginine, Histidine and Methionine act as strong hubs at high interaction cutoffs whereas the hydrophobic Leucine and Isoleucine residues get added to these hubs at low interaction cutoffs, forming weak hubs. The hubs identified are found to play a role in bringing together different secondary structural elements in the tertiary structure of the proteins. They are also found to contribute to the additional stability of the thermophilic proteins and hence could be crucial for the folding and stability of the unique three-dimensional structure of proteins.

Key Words: Amino acid hubs, Largest cluster, Network topology of protein structures, Non-covalent interaction strength, Protein structure graphs, Stability of thermophilic proteins

This article has been cited by other articles:

				G. Bagler and S. Sinha Assortative mixing in Protein Contact Networks and protein folding kinetics Bioinformatics, July 15, 2007; 23(14): 1760 - 1767. [Abstract] [Full Text] [PDF]

				Md. Aftabuddin and S. Kundu Hydrophobic, Hydrophilic, and Charged Amino Acid Networks within Protein Biophys. J., July 1, 2007; 93(1): 225 - 231. [Abstract] [Full Text] [PDF]

				A. Ghosh, K. V. Brinda, and S. Vishveshwara Dynamics of Lysozyme Structure Network: Probing the Process of Unfolding Biophys. J., April 1, 2007; 92(7): 2523 - 2535. [Abstract] [Full Text] [PDF]