David:

In my experience most people don't put a lot of thought into an upper limit for 
van der Waals (VDW) contacts and use a "hard", arbitrary upper value of 4 
Angstrom.

In the mid-1980's, Wayne Hendrickson and I proposed that one should use:

·         Atom type dependent cutoffs

·         As an approximation to the asymptote to zero energy at infinite 
distance, an upper bound that was as much above the distance of minimum energy 
(Rmin) as Rmin was above the zero energy, Rzero, which is the point at which 
the repulsive forces exceed the attractive forces. Using a form of a 6-12 
potential, we calculated that Rlimit = 1.11 x Rmin (and that Rzero = 0.89 x 
Rmin).

I have used that in all my succeeding work, e.g. on antibodies, although during 
a stint in David Davies' group at NIH following working with Wayne at the Naval 
Research Laboratory, I switched from using the very simple 4 atom types that 
PROTIN used to a somewhat more complex set of values that I was introduced to 
based on a paper by Gelin & Karplus (1979).

Here are some references:

S. Sheriff, W. A. Hendrickson & J. L. Smith (1987).  The Structure of 
Myohemerythrin in the Azidomet State at 1.7/1.3 Å Resolution.  J. Mol. Biol. 
197, 273-296.

S. Sheriff (1993).  Some Methods for Examining the Interaction between Two 
Molecules.  Immunomethods 3, 191-196.

B. R. Gelin & M. Karplus (1979).  Side-Chain Torsional Potentials: Effect of 
Dipeptide, Protein, and Solvent Environment.  Biochemistry 18, 1256-1268.

And here are some reviews that used that used this calculation to compare 
structures:

D. R. Davies, E. A. Padlan & S. Sheriff (1990).  Antibody-Antigen Complexes.  
Annu. Rev. Biochem. 59, 439-473.

S. Sheriff (1993). Antibody - Protein Complexes.  Immunomethods 3, 222-227.

Papers on antibody/antigen complexes that were edited by Ian Wilson in his 
capacity as an editor of J. Mol. Biol. were often requested to use the 
methodology as well.  Unfortunately [ ;) ], too many papers appeared outside of 
J. Mol. Biol. that were ignorant of the methodology put in place by me and used 
by Ian's group at Scripps as evidenced by (although these report on buried 
surface area calculations):

I.  A. Wilson & R. L. Stanfield (1993). Antibody-antigen interactions (1993). 
Curr. Opin. Struct. Biol. 3, 113-118.

I.  A. Wilson & R. L. Stanfield (1994). Antibody-antigen interactions: new 
structures and new conformational changes (1994). Curr. Opin. Struct. Biol. 4, 
857-867.

for these methods to remain the standard in the field.

In the department of totally shameless self-promotion (as opposed to the above 
shameless self-promotion), I have published a recent paper, where I have used 
this methodology for the field of 10Fn3-based variants, when used as binding 
proteins in a manner analogous to antibodies, or more similarly, VHH domains 
(Camelid-like VH domains):

V. Ramamurthy, S. R. Krystek, Jr., A. Bush, A. Wei, S. Emanuel, R. DasGupta, A. 
Janjua, Z. Lin, L. Cheng, M. Murdock, D. Cohen, P. Morin, J. H. Davis, M. 
Dabritz, D. C. McLaughlin, K. A. Russo, G. Chao, M. C. Wright, V. A. Jenny, L. 
J. Engle, E. Furfine & S. Sheriff (2012).  Structures of Adnectin/Protein 
complexes reveal an expanded binding footprint.  Structure, 20, 259-269.

Steven


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