A civil engineering model of protein conformational change

We present a variational approach for the simulation of large conformationa l changes of proteins (including multiple protein chains/ligands) which tak es advantage of their cross-linked one-dimensional nature, a structure whic h often occurs in civil engineering. Conformational changes are computed by incremental energy minimisation. We use an efficient finite element method for finding equilibria of complexes composed of inter-linked chains; this method is based on recent advances in the description of one-dimensional el asticity. Protein backbone elasticity, van der Waals repulsions, hydrogen b onds and salt bridges are taken into account, together with user-defined ge ometric distance constraints that may be imposed for purposes of simulating various binding processes based on chemical knowledge. These computational methods have been integrated into a system, Proteinmorphosis, which includ es interactive visualisation. The conformational change of calmodulin upon peptide binding is examined as a first experiment. Allostery in hemoglobin, which consists of a cooperative oxygen binding mechanism, is a second, mor e sophisticated, numerical experiment. Different modelling strategies are d esigned to understand the allostery. The results for both molecules are con sistent with existing hypotheses, and reproduce the known atomic positions after binding to within the experimental error. The modelling system is par t of an on-going program to model structural biology, from protein structur e to cell and tissue properties.