Comparing interfacial dynamics in protein-protein complexes: an elastic network approach

Zen, Andrea; Micheletti, Cristian; Keskin, Ozlem; Nussinov, Ruth
January 2010
BMC Structural Biology;2010, Vol. 10, p26
Academic Journal
Background: The transient, or permanent, association of proteins to form organized complexes is one of the most common mechanisms of regulation of biological processes. Systematic physico-chemical studies of the binding interfaces have previously shown that a key mechanism for the formation/stabilization of dimers is the steric and chemical complementarity of the two semi-interfaces. The role of the fluctuation dynamics at the interface of the interacting subunits, although expectedly important, proved more elusive to characterize. The aim of the present computational study is to gain insight into salient dynamics-based aspects of protein-protein interfaces. Results: The interface dynamics was characterized by means of an elastic network model for 22 representative dimers covering three main interface types. The three groups gather dimers sharing the same interface but with good (type I) or poor (type II) similarity of the overall fold, or dimers sharing only one of the semi-interfaces (type III). The set comprises obligate dimers, which are complexes for which no structural representative of the free form (s) is available. Considerations were accordingly limited to bound and unbound forms of the monomeric subunits of the dimers. We proceeded by first computing the mobility of amino acids at the interface of the bound forms and compare it with the mobility of (i) other surface amino acids (ii) interface amino acids in the unbound forms. In both cases different dynamic patterns were observed across interface types and depending on whether the interface belongs to an obligate or non-obligate complex. Conclusions: The comparative investigation indicated that the mobility of amino acids at the dimeric interface is generally lower than for other amino acids at the protein surface. The change in interfacial mobility upon removing "in silico" the partner monomer (unbound form) was next found to be correlated with the interface type, size and obligate nature of the complex. In particular, going from the unbound to the bound forms, the interfacial mobility is noticeably reduced for dimers with type I interfaces, while it is largely unchanged for type II ones. The results suggest that these structurally- and biologically-different types of interfaces are stabilized by different balancing mechanisms between enthalpy and conformational entropy.


Related Articles

  • Entropy and enthalpy of interaction between amino acid side chains in nanopores. Vaitheeswaran, S.; Thirumalai, D. // Journal of Chemical Physics;12/14/2014, Vol. 141 Issue 22, p1 

    Understanding the stabilities of proteins in nanopores requires a quantitative description of confinement induced interactions between amino acid side chains. We use molecular dynamics simulations to study the nature of interactions between the side chain pairs ALA-PHE, SER-ASN, and LYS-GLU in...

  • Optimal design of thermally stable proteins. Ryan M. Bannen; Vanitha Suresh; George N. Phillips; Stephen J. Wright; Julie C. Mitchell // Bioinformatics;Oct2008, Vol. 24 Issue 20, p2339 

    Motivation: For many biotechnological purposes, it is desirable to redesign proteins to be more structurally and functionally stable at higher temperatures. For example, chemical reactions are intrinsically faster at higher temperatures, so using enzymes that are stable at higher temperatures...

  • USF2.  // Encyclopedic Reference of Cancer;2001, p945 

    A definition of the term "USF2" is presented. It refers to a protein member of the Usf family of amino acids. Usf2-DNA binding requires dimerization with another protein, either as a homodimer or a heterodimer.

  • Asymmetric interactions in the adenosine-binding pockets of the MS2 coat protein dimer. Powell, Amy J.; Peabody, David S. // BMC Molecular Biology;2001, Vol. 2, p6 

    Background: The X-ray structure of the MS2 coat protein-operator RNA complex reveals the existence of quasi-synmetric interactions of adenosines -4 and -10 in pockets formed on different subunits of the coat protein dimer. Both pockets utilize the same five amino acid residues, namely Val29,...

  • Similarity Analysis of Protein Sequences Based on the Normalized Relative-Entropy. Chun Li; Jùn Wang; Yi Zhang; Jūn Wang // Combinatorial Chemistry & High Throughput Screening;Jul2008, Vol. 11 Issue 6, p477 

    Based on the classification of 20 amino acids, we reduce a protein primary sequence to six (0,1) sequences. For each of them, two so-called normalized relative-entropies are calculated and thus a 12-D vector is constructed to describe the protein primary sequence. The examination of...

  • Propensity of Amino Acids in Loop Regions Connecting Beta-Strands. Minuchehr, Z.; Goliaei, B. // Protein & Peptide Letters;May2005, Vol. 12 Issue 4, p379 

    The fact that loops assume important roles in molecular functions and biological recognition is well known. In this study the Propensity and the Relative entropy of amino-acids in loop structures connecting beta-strands are calculated. Results showed that Asn is the most frequently occurring...

  • Structural Patterns in α Helices and β Sheets in Globular Proteins. Bhattacharjee, Nicholus; Biswas, Parbati // Protein & Peptide Letters;Aug2009, Vol. 16 Issue 8, p953 

    Secondary structural elements like α-helix and β-sheet constitute the major components of proteins. Here we present a systematic position wise analysis of the structural and sequence characteristics of alpha-helices and beta-sheets. Helix and sheet are found to follow a complementary...

  • Using the Concept of Chou's Pseudo Amino Acid Composition to Predict Apoptosis Proteins Subcellular Location: An Approach by Approximate Entropy. Xiaoying Jiang; Rong Wei; Tongliang Zhang; Quan Gu // Protein & Peptide Letters;May2008, Vol. 15 Issue 4, p392 

    The function of protein is closely correlated with it subcellular location. Prediction of subcellular location of apoptosis proteins is an important research area in post-genetic era because the knowledge of apoptosis proteins is useful to understand the mechanism of programmed cell death....

  • Critical Factors Governing the Difference in Antizyme-Binding Affinities between Human Ornithine Decarboxylase and Antizyme Inhibitor. Yen-Chin Liu; Yi-Liang Liu; Jia-Yang Su; Guang-Yaw Liu; Hui-Chih Hung // PLoS ONE;2011, Vol. 6 Issue 4, p1 

    Both ornithine decarboxylase (ODC) and its regulatory protein, antizyme inhibitor (AZI), can bind with antizyme (AZ), but the latter has a higher AZ-binding affinity. The results of this study clearly identify the critical amino acid residues governing the difference in AZ-binding affinities...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics