Abstract
The many-body physics of hydrogen bond formation in alpha-helices of globular proteins was investigated using a simple physics-based model. Specifically, a context-sensitive hydrogen bond potential, which depends on residue identity and degree of solvent exposure, was used in the framework of the Associated Memory Hamiltonian codes developed previously but without using local-sequence structure matches ("memories"). Molecular dynamics simulations employing the energy function using the context-sensitive hydrogen bond potential alone (the "amnesiac" model) were used to generate low energy structures for three alpha-helical test proteins. The resulting structures were compared to both the X-ray crystal structures of the test proteins and the results obtained using the full Associated Memory Hamiltonian previously used. Results show that the amnesiac Hamiltonian was able to generate structures with reasonably high structural similarity (Q approximately 0.4) to that of the native protein but only with the use of predicted secondary structure information encoding local steric signals. Low energy structures obtained using the amnesiac Hamiltonian without any a priori secondary structure information had considerably less similarity to the native protein structures (Q approximately 0.3). Both sets of results utilizing the amnesiac Hamiltonian are poorer than when local-sequence structure matches are used.