+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Role of long- and short-range hydrophobic, hydrophilic and charged residues contact network in protein's structural organization

Role of long- and short-range hydrophobic, hydrophilic and charged residues contact network in protein's structural organization

Bmc Bioinformatics 13: 142

The three-dimensional structure of a protein can be described as a graph where nodes represent residues and the strength of non-covalent interactions between them are edges. These protein contact networks can be separated into long and short-range interactions networks depending on the positions of amino acids in primary structure. Long-range interactions play a distinct role in determining the tertiary structure of a protein while short-range interactions could largely contribute to the secondary structure formations. In addition, physico chemical properties and the linear arrangement of amino acids of the primary structure of a protein determines its three dimensional structure. Here, we present an extensive analysis of protein contact subnetworks based on the London van der Waals interactions of amino acids at different length scales. We further subdivided those networks in hydrophobic, hydrophilic and charged residues networks and have tried to correlate their influence in the overall topology and organization of a protein. The largest connected component (LCC) of long (LRN)-, short (SRN)- and all-range (ARN) networks within proteins exhibit a transition behaviour when plotted against different interaction strengths of edges among amino acid nodes. While short-range networks having chain like structures exhibit highly cooperative transition; long- and all-range networks, which are more similar to each other, have non-chain like structures and show less cooperativity. Further, the hydrophobic residues subnetworks in long- and all-range networks have similar transition behaviours with all residues all-range networks, but the hydrophilic and charged residues networks don't. While the nature of transitions of LCC's sizes is same in SRNs for thermophiles and mesophiles, there exists a clear difference in LRNs. The presence of larger size of interconnected long-range interactions in thermophiles than mesophiles, even at higher interaction strength between amino acids, give extra stability to the tertiary structure of the thermophiles. All the subnetworks at different length scales (ARNs, LRNs and SRNs) show assortativity mixing property of their participating amino acids. While there exists a significant higher percentage of hydrophobic subclusters over others in ARNs and LRNs; we do not find the assortative mixing behaviour of any the subclusters in SRNs. The clustering coefficient of hydrophobic subclusters in long-range network is the highest among types of subnetworks. There exist highly cliquish hydrophobic nodes followed by charged nodes in LRNs and ARNs; on the other hand, we observe the highest dominance of charged residues cliques in short-range networks. Studies on the perimeter of the cliques also show higher occurrences of hydrophobic and charged residues' cliques. The simple framework of protein contact networks and their subnetworks based on London van der Waals force is able to capture several known properties of protein structure as well as can unravel several new features. The thermophiles do not only have the higher number of long-range interactions; they also have larger cluster of connected residues at higher interaction strengths among amino acids, than their mesophilic counterparts. It can reestablish the significant role of long-range hydrophobic clusters in protein folding and stabilization; at the same time, it shed light on the higher communication ability of hydrophobic subnetworks over the others. The results give an indication of the controlling role of hydrophobic subclusters in determining protein's folding rate. The occurrences of higher perimeters of hydrophobic and charged cliques imply the role of charged residues as well as hydrophobic residues in stabilizing the distant part of primary structure of a protein through London van der Waals interaction.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 055607332

Download citation: RISBibTeXText

PMID: 22720789

DOI: 10.1186/1471-2105-13-142

Related references

Long-range and short-range mechanisms of hydrophobic attraction and hydrophilic repulsion in specific and aspecific interactions. Journal of Molecular Recognition 16(4): 177-190, 2003

Identification of short-range structural interactions between transmembrane charged residues in shaker K+ channels. Biophysical Journal 70(2 Part 2): A12, 1996

Role of Hydrophobic Clusters and Long-Range Contact Networks in the Folding of (/)8 Barrel Proteins. Biophysical Journal 84(3): 1919-1925, 2003

Hydrophobic, hydrophilic, and charged amino acid networks within protein. Biophysical Journal 93(1): 225-231, 2006

Short-range contact preferences and long-range indifference: is protein folding stoichiometry driven?. Journal of Biomolecular Structure and Dynamics 28(4): 603-5; Discussion 669-674, 2011

The Role of Charged Residues in the Structural Adaptation of Short-Chain Alcohol Dehydrogenase (Sdr) from Thermophilic Organisms to High Temperatures. Moscow University Chemistry Bulletin 73(5): 231-236, 2018

Role of hydrophobic clusters and long-range contact networks in the folding of (alpha/beta)8 barrel proteins. Biophysical Journal 84(3): 1919-1925, 2003

Is it possible for short peptide composed of positively- and negatively-charged "hydrophilic" amino acid residue-clusters to form metastable "hydrophobic" packing?. Physical Chemistry Chemical Physics 2019, 2019

Introduction of short-range restrictions in a protein-folding algorithm involving a long-range geometrical restriction and short-, medium-, and long-range interactions. Proceedings of the National Academy of Sciences of the United States of America 78(11): 6584-6587, 1981

Lysine Scanning of Arg 10 -Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues. Acs Omega 1(6): 1262-1265, 2016

Role of charged and hydrophobic residues in the oligomerization of the PYRIN domain of ASC. Biochemistry 44(2): 575-583, 2005

Role of the hydrophobic and charged residues in the 218-226 region of apoA-I in the biogenesis of HDL. Journal of Lipid Research 54(12): 3281-3292, 2014

NPPD: A Protein-Protein Docking Scoring Function Based on Dyadic Differences in Networks of Hydrophobic and Hydrophilic Amino Acid Residues. Biology 4(2): 282-297, 2015

Hydrophobic and Hydrophilic Residues are Important for Small Molecule Binding to the Intrinsically Disordered Protein c-Myc. Biophysical Journal 104(2): 52a-53a, 2013

Analysis of hydrophobic and charged patches and influence of medium- and long-range interactions in molecular chaperones. Biophysical Chemistry 75(2): 105-113, Nov 16, 1998