Myosin-binding protein C (MyBP-C) is a myofibril-associated protein found in cardiac and skeletal muscle. The cardiac isoform (cMyBP-C) is subject to reversible phosphorylation and the surface-charge state of the protein is of keen interest with regard to understanding the inter-protein interactions that are implicated in its function. Diffraction data from the C1 domain of cMyBP-C were extended to 1.30 angstrom resolution, where the of the diffraction data crosses 2.0, using intense synchrotron radiation. The protonation-state determinations were not above 2 sigma (the best was 1.81 sigma) and therefore an extrapolation is given, based on 100% data completeness and the average DPI, that a 3 sigma determination could be possible if X-ray data could be measured to 1.02 angstrom resolution. This might be possible via improved crystallization or multiple sample evaluation, e. g. using robotics or a yet more intense/collimated X-ray beam or combinations thereof. An alternative would be neutron protein crystallography at 2 angstrom resolution, where it is estimated that for the unit-cell volume of the cMyBP-C C1 domain crystal a crystal volume of 0.10 mm(3) would be needed with fully deuterated protein on LADI III. These efforts would optimally be combined in a joint X-ray and neutron model refinement. ; Fisher, S. J. Helliwell, J. R. Khurshid, S. Govada, L. Redwood, C. Squire, J. M. Chayen, N. E. 18 BLACKWELL PUBLISHING OXFORD Part 6 301BG