jp8b05791_si_001.pdf (1.42 MB)
AWSEM-IDP: A Coarse-Grained Force Field for Intrinsically Disordered Proteins
journal contribution
posted on 2018-08-09, 18:25 authored by Hao Wu, Peter G. Wolynes, Garegin A. PapoianThe
associative memory, water-mediated, structure and energy model (AWSEM)
has been successfully used to study protein folding, binding, and
aggregation problems. In this work, we introduce AWSEM-IDP, a new
AWSEM branch for simulating intrinsically disordered proteins (IDPs),
where the weights of the potentials determining secondary structure
formation have been finely tuned, and a novel potential is introduced
that helps to precisely control both the average extent of protein
chain collapse and the chain’s fluctuations in size. AWSEM-IDP
can efficiently sample large conformational spaces, while retaining
sufficient molecular accuracy to realistically model proteins. We
applied this new model to two IDPs, demonstrating that AWSEM-IDP can
reasonably well reproduce higher-resolution reference data, thus providing
the foundation for a transferable IDP force field. Finally, we used
thermodynamic perturbation theory to show that, in general, the conformational
ensembles of IDPs are highly sensitive to fine-tuning of force field
parameters.