Molecular dynamics simulation combined with small‐angle X‐ray/neutron scattering defining solution‐state protein structures

Protein crystallography is frequently used to obtain the atomic‐resolution structure of a particular protein by x‐ray diffraction of its crystallized form. Nevertheless, a single static structure cannot represent the sequence structural dynamics of a protein's function. Based on our previous study (J. Phys. Chem. B 2017, 121 (50), 11229–11240 and ACS Catal. 2018, 8 (3), 2534–2545), we herein introduce a strategy of determining the protein hydration structures by small‐angle X‐ray and neutron scattering (SAXS and SANS) with contrast variation techniques, in combination with molecular dynamics simulation (MD), to describe hydrodynamics conformation transitions of biomacromolecules. Water is a partner that conducts the dynamics of proteins, and hydration interactions with proteins affect their dynamics. To shed light on the way of the chemical constitution of a protein, the water interactions, and the dynamics of its structure underlie the specific mechanisms of enzyme functions, we review an integrated approach using small‐angle X‐ray and neutron scattering (SAXS and SANS) in combination with molecular dynamics (MD) simulation to probe the structural dynamics of a given protein, thus shedding light on its function. We herein introduce a combination approach in determining the protein structure‐dynamics‐function in solution through small‐angle X‐ray and neutron scattering (SAXS and SANS) contrast variation, combined with multi‐scale molecular dynamics simulations to describe the hydrodynamics conformation transitions of biomacromolecules in the facilities of synchrotron/neutron beamline stations (TLS 23A and TPS 13A at NSRRC, Taiwan/QUOKKA and BILBY at ANSTO, Australia).