Method for distance measurements with solid-state NMR

A method for determining one or more distances in a solid-state sample comprising one or more molecules, said one or more molecules comprising one or more pairs of sites, each said pair of sites comprising a first site and a second site, each said distance being between said first and said second site, said method comprising:

• a. binding one or more of said one or more molecules to one or more target compounds;
• b. generating NMR time-domain data from NMR active nuclei, wherein each pair of said one or more pairs of sites has said first site occupied by a first NMR active nucleus and has said second site occupied by a second NMR active nucleus, wherein said first NMR active nucleus is observed in said generating step and said second NMR active nucleus has a chemical shift, and said first and second NMR active nuclei have a dipolar coupling characterized by a dipolar coupling frequency responsive to the distance between said first and second sites, and said time-domain data being is responsive along at least one first time dimension to said dipolar coupling of each said one or more pairs and along at least one second time dimension to said chemical shift of said second NMR active nuclei at said second site of said one or more pairs of sites;
• c. analyzing said NMR time-domain data to obtain spectral-domain data identifying said one or more dipolar coupling frequencies characterizing said dipolar couplings between said first and said second nuclei in said one or more pairs of sites, said analyzing comprising applying a REDOR transform to said time-domain data along said first time dimension;
• d. identifying, for each said dipolar coupling frequency, said one or more chemical shifts of each said second NMR active nucleus with that dipolar coupling frequency;
• and
• e. calculating one or more distances between said pairs of sites based on said one or more dipolar coupling frequencies.

A method for determining one or more distances in a solid-state sample comprising one or more peptides, said one or more peptides comprising one or more pairs of sites, each said pair of sites comprising a first site and a second site, each said distance being between said first and said second site, said method comprising:

• a. generating NMR time-domain data from NMR active nuclei, wherein each pair of said one or more pairs of sites has said first site occupied by a first NMR active nucleus and has said second site occupied by a second NMR active nucleus, wherein said first NMR active nucleus is observed in said generating step and said second NMR active nucleus has a chemical shift, and said first and second NMR active nuclei have a dipolar coupling characterized by a dipolar coupling frequency responsive to the distance between said first and second sites, and said time-domain data being is responsive along at least one first time dimension to said dipolar coupling of each said one or more pairs and along at least one second time dimension to said chemical shift of said second NMR active nuclei at said second site of said one or more pairs of sites;
• b. analyzing said NMR time-domain data to obtain spectral-domain data identifying said one or more dipolar coupling frequencies characterizing said dipolar couplings between said first and said second nuclei in said one or more pairs of sites, said analyzing comprising applying a REDOR reform to said time-domain data along said first time dimension;
• c. identifying, for each said dipolar coupling frequency, said one or more chemical shifts of each said second NMR active nucleus with that dipolar coupling frequency;
• and
• d. calculating one or more distances between said pairs of sites based on said one or more dipolar coupling frequencies.

A method for determining a plurality of distances in a solid-state sample comprising one or more molecules, said one or more molecules comprising a plurality of pairs of sites, each said pair of sites comprising a first site and a second site, each said distance being between said first and said second site, said method comprising:

• a. generating NMR time-domain data from NMR active nuclei, wherein each pair of said one or more pairs of sites has said first site occupied by a first NMR active nucleus and has said second site occupied by a second NMR active nucleus, wherein said first NMR active nucleus is observed in said generating step and said second NMR active nucleus has a chemical shift, and said first and second NMR active nuclei have a dipolar coupling characterized by a dipolar coupling frequency responsive to the distance between said first and second sites, and said time-domain data is responsive along at least one first time dimension to said dipolar coupling of each said one or more pairs and along at least one second time dimension to said chemical shift of said second NMR active nuclei at said second site of said one or more pairs of sites;
• b. analyzing said NMR time-domain data to obtain spectral-domain data identifying said one or more dipolar coupling frequencies characterizing said dipolar couplings between said first and said second nuclei in said one or more pairs of sites, said analyzing comprising applying a REDOR transform to said time-domain data along said first time dimension;
• c. identifying, for each said dipolar coupling frequency, said one or more chemical shifts of each said second NMR active nucleus with that dipolar coupling frequency;
• and
• d. calculating one or more distances between said pairs of sites based on said one or more dipolar coupling frequencies.

A method for determining one or more distances in a solid-state sample comprising one or more molecules, said one or more molecules comprising one or more pairs of sites, each said pair of sites comprising a first site and a second site, each said distance being between said first and said second site, said method comprising:

• a. generating NMR time-domain data from NMR active nuclei, wherein each pair of said one or more pairs of sites has said first site occupied by a first NMR active nucleus and has said second site occupied by a second NMR active nucleus, wherein said first NMR active nucleus is observed in said generating step and has a chemical shift, and said first and second NMR active nuclei form a pair of NMR active nuclei and have a dipolar coupling characterized by a dipolar coupling frequency responsive to the distance between said first and second sites, and said time-domain data is responsive along at least one first time dimension to said dipolar coupling of each said one or more pairs and is responsive along at least one second time dimension to said chemical shift of said first nucleus at said first sites of each said one or more pairs;
• b. analyzing said NMR time-domain data to obtain spectral-domain data identifying said one or more dipolar coupling frequencies characterizing said dipolar couplings between said first and said second nuclei in said one or more pairs of sites, and identifying for each said dipolar coupling frequency the chemical shift of each said first nucleus with that dipolar coupling frequency, said analyzing comprising applying a dipolar-dephasing spectral transform to said time-domain data along said first time dimension and along other time dimensions as are responsive to said one or more dipolar couplings;
• and
• c. calculating one or more distances between said pairs of sites based on said one or more dipolar coupling frequencies.