Most importantly, many of the inherent motions in proteins occur on the time scales of central biochemical processes[7-9]:

1. Vibrations and local motions (10-15-10-10 s)—correspond to chemical events that occur during enzyme-mediated catalysis. ese include:

• e making or breaking of covalent bonds (10-14-10-10 s)

• Formation of hydrogen bonds (10-12-10-10 s)

• Transfer of electrons/protons/hydride ions between chemical groups (10-12 s = 1 ps)


2. Motions of side-chains, secondary elements and domains (10-9-10-3 s)— correspond to the following:

• Proton transport (10-9-10-4 s)

• Electron tunneling (10-9-10-4 s)

• Water structure reorganization (10-8 s)

• Ligand binding (10-8-10 s)

• Local denaturation (10-5-10 s)

• Allostery (10-5-1 s)

is implies what most protein scientists today agree, which is that the inherent dynamics of proteins are important for their function. Indeed, when a protein’s dynamics are slowed down by a decrease in temperature, its activity diminishes as well. Most of the more detailed evidence connecting protein dynamics and function is based on observations carried out on relatively long time scales. For example, in many enzymes the rate of catalysis is determined by conformational changes needed for the correct positioning of catalytic residues with respect to the substrate; these changes occur at the secondary structure level.[9] Another example is substrate/ligand-binding (or releasing) processes, which require conformational changes leading to the opening or closing of protein segments acting as gates. Indeed, many enzymes tend to undergo dynamic changes that close the binding site upon substrate binding.[10] is completely or partially prevents solvent access to the binding site, thus strengthening protein-ligand electrostatic interactions that may be important for catalysis, and also reducing the solvent’s ability to interact with the substrate at the expense of binding site groups (competing interactions). Although all of the above represent longrange dynamics, short motions in proteins, from concerted vibrations of covalent bonds

to motions of small side-chains, are also known to contribute to the overall dynamics and function of the protein.