Direct use of 15N relaxation rates as experimental restraints on molecular shape and orientation for docking of protein-protein complexes.
(15)N relaxation rates contain information on overall molecular shape and size, as well as residue specific orientations of N-H bond vectors relative to the axes of the diffusion tensor. Here we describe a pseudopotential E(relax) that permits direct use of (15)N relaxation rates, in the form of R(2)/R(1) ratios, as experimental restraints in structure calculations without requiring prior information to be extracted from a known molecular structure. The elements of the rotational diffusion tensor are calculated from the atomic coordinates at each step of the structure calculation and then used together with the N-H bond vector orientations to compute the (15)N R(2)/R(1) ratios. We show that the E(relax) term can be reliably used for protein-protein docking of complexes and illustrate its applicability to the 40 kDa complex of the N-terminal domain of enzyme I and the histidine phosphocarrier protein HPr and to the symmetric HIV-1 protease dimer.
Ryabov
Yaroslav
Y
Division of Computational Bioscience, Building 12A, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20892-5624, USA.
Clore
G Marius
GM
Schwieters
Charles D
CD
D009587:Nitrogen Isotopes / Q000737:chemistry*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
D009587:Nitrogen Isotopes; D011506:Proteins
Proteomics. 2009 Dec;9(23):5224-32
19834907
Protein Eng. 1988 Apr;2(1):27-38
2855369
J Biol Chem. 1993 Oct 25;268(30):22490-501
8226757
Methods Enzymol. 2001;339:127-74
11462810
J Am Chem Soc. 2006 Dec 6;128(48):15432-44
17132010
Structure. 1996 Jul 15;4(7):861-72
8805571
Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18464-9
17116869
Trends Biotechnol. 1998 Jan;16(1):22-34
9470228
J Biomol NMR. 1996 Oct;8(3):273-84
8953218
Nat Struct Biol. 1997 Jun;4(6):443-9
9187651
Proteins. 2007 Dec 1;69(4):726-33
17803234
Nat Struct Biol. 1999 Feb;6(2):166-73
10048929
J Am Chem Soc. 2003 Mar 12;125(10):2902-12
12617657
Curr Opin Struct Biol. 2009 Apr;19(2):164-70
19327983
J Magn Reson. 2001 Oct;152(2):288-302
11567582
J Am Chem Soc. 2003 Feb 19;125(7):1731-7
12580598
Proteins. 2007 Dec 1;69(4):704-18
17918726
J Am Chem Soc. 2009 Jul 15;131(27):9522-31
19537713