Protein as a Flexible Structure: Case Study of the HIV-Protease

Michal Kolář¹, Michele Leone², Cristian Micheletti¹, and Riccardo Zecchina³

¹SISSA and INFM, Via Beirut 2-4, Trieste, Italy

²ISI, Viale Settimio Severo 65, Torino, Italy

³ICTP, Strada Costiera 11, Trieste, Italy

kolarmi@sissa.it

In order to find properties of the minimal model of protein flexibility, we introduce a two-variable coarse-grained model describing the rigidity of a three-dimensional structure—protein. We follow local changes of rigidity after removing a certain fraction of contact interactions among amino-acid residues. In this way, mobility of a single residue may be estimated. The model is mapped to a constraint satisfaction problem and solved via the Belief Propagation iterative message–passing algorithm.

For the HIV protease, the resulting flexibility profiles are compared with the experimental temperature factors data, burial profile predictions and Molecular Dynamics simulations. Although we cannot estimate the actual presence or absence of a physical interaction between specific residues, we show that the contact interactions in the HIV protease are distributed in the way that maximizes the overall flexibility of the protein. This confirms the notion of the HIV Protease as a flexible albeit compactly folded structure.