Flexibility as part of the geometric filtering problem.

Ludwig Krippahl, Universidade Nova de Lisboa.
 

When modelling protein complexes, geometric complementarity is generally the most important criterion for filtering the large set of possible models and reducing it to a manageable sub-set. This necessary reliance on geometry makes protein flexibility a major problem. Two solutions for this problem are either to account for flexibility implicitly by relaxing the stringency of the filter, or to retain a stringent filter and model different conformations explicitly. Though the latter approach has become more popular with the increase in computation power, we propose that, in many cases, flexibility can be considered as part of the general problem of the reliability geometric complementarity as a predictor of protein interaction.

To this end, our docking algorithm BiGGER [1] uses an implicit representation of protein flexibility that can distinguish rigid and flexible regions, and can incorporate experimental data as an additional filter to compensate the lower stringency of the geometric complementarity filter [2].
 

[1] Palma, P.N., Krippahl, L.,Wampler, J.W., Moura, J.G., A New (Soft) Docking Algorithm for Predicting Protein Interactions. Protein:Struc. 
Func. Gen. 2000 Jun 1;39(4):372-84.

[2] Krippahl, L., Moura, J.J., Palma, P.N., Modeling Protein Complexes with BiGGER. Prot: Struc.Funct. Gen, V. 52(1):19-23.