2 resultados para CDC42
em Chinese Academy of Sciences Institutional Repositories Grid Portal
Resumo:
Combining a single-molecule study of protein binding with a coarse grained molecular dynamics model including solvent (water molecules) effects, we find that biomolecular recognition is determined by flexibilities in addition to structures. Our single-molecule study shows that binding of CBD (a fragment of Wiskott-Aldrich syndrome protein) to Cdc42 involves bound and loosely bound states, which can be quantitatively explained in our model as a result of binding with large conformational changes. Our model identified certain key residues for binding consistent with mutational experiments. Our study reveals the role of flexibility and a new scenario of dimeric binding between the monomers: first bind and then fold.
Resumo:
The study of associations between two biomolecules is the key to understanding molecular function and recognition. Molecular function is often thought to be determined by underlying structures. Here, combining a single-molecule study of protein binding with an energy-landscape-inspired microscopic model, we found strong evidence that biomolecular recognition is determined by flexibilities in addition to structures. Our model is based on coarse-grained molecular dynamics on the residue level with the energy function biased toward the native binding structure ( the Go model). With our model, the underlying free-energy landscape of the binding can be explored. There are two distinct conformational states at the free-energy minimum, one with partial folding of CBD itself and significant interface binding of CBD to Cdc42, and the other with native folding of CBD itself and native interface binding of CBD to Cdc42. This shows that the binding process proceeds with a significant interface binding of CBD with Cdc42 first, without a complete folding of CBD itself, and that binding and folding are then coupled to reach the native binding state.
