DISTANCE CONSTRAINTS ON MACROMOLECULAR CONFORMATION

Abstract

Many physico-chemical studies are made on proteins to determine something of their solution conformation. The coat protein of tobacco mosaic virus was subjected to more non-crystallographic experimental studies to determine its native conformation than perhaps any other protein, yet the sum of the experimentally determined constraints on its tertiary structure are surprisingly inadequate to fix its conformation. Minor inconsistencies in the data were detected and removed and a sampling of conformations consistent with all the data, which differ among themselves by r.m.s. [root mean square] deviations of the respective interresidue distances ranging from 5.7 .ANG. to 15.8 .ANG., was calculated. Some individual inter-residue distances differ by as much as 50 .ANG. from structure to structure. To restrict the range of possible conformations to something corresponding to the errors in a 10 .ANG. resolution X-ray crystal structure, chemical and spectroscopic studies must be much more detailed than anything done to date. These calculations appear useful in deciding which further experiments would be most productive.