A simple genetic algorithm for the optimization of multidomain protein homology models driven by NMR residual dipolar coupling and small angle X-ray scattering data
Most proteins comprise several domains and/or participate in functional complexes. Owing to ongoing structural genomic projects, it is likely that it will soon be possible to predict, with reasonable accuracy, the con- served regions of most structural domains. Under these circumstances, it will be important to have methods, based on simple-to-acquire experimental data, that allow to build and reﬁne structures of multi-domain proteins or of protein complexes from homology models of the individual do- mains/proteins. It has been recently shown that small angle X-ray scattering (SAXS) and NMR residual dipolar cou- pling (RDC) data can be combined to determine the architecture of such objects when the X-ray structures of the domains are known and can be considered as rigid objects. We developed a simple genetic algorithm to achieve the same goal, but by using homology models of the domains considered as deformable objects. We applied it to two model systems, an S1KH bi-domain of the NusA protein and the cS-crystallin protein. Despite its simplicity our algorithm is able to generate good solutions when driven by SAXS and RDC data.