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Bioinformatics  
In the post-genomic era, it has become increasingly important to develop efficient analytical techniques to assess structure and function from sequence information. We developed several sequence-based methods and servers to this aim. Yet, it is widely recognized that we need information beyond sequence and even structure to gain insights into the machinery of biomolecules. Our goal is to systematically explore and establish the link between:

sequence patterns/covariance (P2P server (1-2))
structural/functional dynamics (ANM server (3))

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The analysis of correlated mutations in HIV-1 protease is a recent study along these lines. Spectral clustering of sequence covariance matrix is shown therein to identify two clusters of co-evolving amino acids corresponding to neutral mutations and multidrug resistance sites (2). Likewise, the NEF-binding residues on the ATPase domain of Hsp70 are observed to exhibit high co-evolutionary propensities, in addition to their enhanced mobility, suggesting that sequence adaptability and conformational mobility are functional properties that enable NEF recognition and effective binding (4).

References:

1. Eyal E, Pietrokovski S, Bahar I. (2007) Rapid Assessment of Correlated Amino Acids from Pair-to-Pair (P2P) Substitution Matrices Bioinformatics 23, 1837-39

2. Liu Y, Eyal E. & Bahar I (2008) Analysis of correlated mutations in HIV-1 protease using spectral clustering Bioinformatics 24, 1243-1250.

3. Eyal E, Yang LW, Bahar I (2006) Anisotropic network model: systematic evaluation and a new web interface,  Bioinformatics 22, 2619-2627.

4. Liu Y, Gierasch LM, Bahar I. (2010).Role of Hsp70 ATPase domain intrinsic dynamics and sequence evolution in enabling its functional interactions with NEFs,  PLoS Comput Biol 6, e1000931.