A potential function for conformational analysis of proteins

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Abstract
A residue-residue potential function for low resolution protein conformational calculations was devised. The interactions between residues near in sequence maintain correct secondary structure, while the long-range terms in the potential govern the larger packing features and overall globularity. The short-range terms were calculated by comparing the observed distributions of distances between C.alpha. [.alpha. carbon] atoms in 35 protein crystal structures to the expected distributions and assigning the discrepancies to a Boltzmann distribution due to an effective potential. Long-range terms were adjusted to ensure that the crystal structure of bovine pancreatic trypsin inhibitor has a lower total energy than perturbed conformations of the same molecule. Thus the empirical potential function implicitly contains solvation and conformational entropy effects along with the usual Van der Waals and electrostatic energies. Extensive testing of the potential on trypsin inhibitor and other proteins establishes that it is generally applicable to small proteins; it does not attempt to compress or expand the conformations found by X-ray crystallography; standard secondary structural features were maintained under the potential; and there are so many local minima that local minimization can be trusted to return a perturbed structure to the native conformation only if they differ initially by < 1 .ANG.